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Jeffrey W. Innis - One of the best experts on this subject based on the ideXlab platform.

  • molecular characterization of HOXA13 polyalanine expansion proteins in hand foot genital syndrome
    American Journal of Medical Genetics Part A, 2007
    Co-Authors: Boris Utsch, Michael Ludwig, Colleen D Mccabe, Kenneth Galbraith, Ricardo Gonzalez, Mark Born, Jorg Dotsch, Heiko Reutter, Jeffrey W. Innis
    Abstract:

    We report on a father and daughter with hand-foot-genital syndrome (HFGS) with typical skeletal and genitourinary anomalies due to a 14-residue polyalanine expansion in HOXA13. This is the largest (32 residues) polyalanine tract so far described for any polyalanine mutant protein. Polyalanine expansion results in protein misfolding, cytoplasmic aggregation and degradation; however, HOXA13 polyalanine expansions appear to act as loss of function mutations in contrast to gain of function for HOXD13 polyalanine expansions. To address this paradox we examined the cellular consequences of polyalanine expansions on HOXA13 protein using COS cell transfection and immunocytochemistry. HOXA13 polyalanine expansion proteins form cytoplasmic aggregates, and distribution between cytoplasmic aggregates or the nucleus is polyalanine tract size-dependent. Geldanamycin, an Hsp90 inhibitor, reduces the steady-state abundance of all polyalanine-expanded proteins in transfected cells. We also found that wild-type HOXA13 or HOXD13 proteins are sequestered in HOXA13 polyalanine expansion cytoplasmic aggregates. Thus, the difference between HOXA13 polyalanine expansion loss-of-function and HOXD13 polyalanine expansion dominant-negative effect is not the ability to aggregate wild-type group 13 paralogs but perhaps to variation in activities associated with refolding, aggregation or degradation of the proteins.

  • Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability.
    Developmental biology, 2005
    Co-Authors: Thomas M. Williams, Melissa E. Williams, Rork Kuick, David E. Misek, Kevin T. Mcdonagh, Samir M. Hanash, Jeffrey W. Innis
    Abstract:

    Abstract Hox genes encode transcription factors that regulate the morphogenesis of developing embryos. In mammals, knowledge of the genetic pathways, including the possible direct or indirect targets, regulated by HOX proteins is extremely limited. To identify the downstream genes regulated by posterior HOX proteins, we expressed HOXA13 in mouse embryonic fibroblasts lacking paralog group 13 expression using a bicistronic HOXA13/EGFP retroviral vector. Microarray analysis identified 68 genes with significant, reproducible RNA expression changes (50 activated; 18 repressed) in stable HOXA13-expressing cells. Genes with the GO annotation terms “extracellular matrix” and “basement membrane” were greatly overrepresented, and several were shown to be regulated by HOX proteins in other studies. Among the genes strongly activated by HOXA13 were Enpp2, a bifunctional enzyme known to modulate tumor and normal cell motility and which is expressed in precartilaginous condensations; Fhl1, a transcription factor implicated in muscle cell differentiation and development; and M32486, a putative integral membrane molecule expressed in the female reproductive tract. Expression differences in the HOXA13-expressing cells were confirmed for selected downstream genes using semi-quantitative RT-PCR, and in vivo coexpression with HOXA13 in the limb interdigital mesenchyme was demonstrated for many. For two candidates, Igfbp4 and Fstl, interdigital limb bud expression was reduced in HOXA13 mutants. To explore whether paralogous and nonparalogous HOX proteins could regulate the same genes, we created new HOX cell lines and examined the expression of selected genes identified by the HOXA13 screen. HOXD13 similarly activated/repressed 6 tested candidates, demonstrating that multiple downstream genetic pathways may be regulated by paralog HOX proteins. In contrast, HOXA9 was only able to repress expression of some gene targets. A HOXD13 mutant, HOXD13IQN > AAA, incapable of monomeric DNA-binding, activated the expression of 5 HOXA13-upregulated genes; but was incapable of repressing the expression of Ngef and Casp8ap2. Our results suggest that HOX protein–protein interactions without direct HOX DNA-binding may play a larger role in HOX transcriptional regulation than generally assumed, and DNA-binding appears critical for repression.

  • Range of HOX/TALE Superclass Associations and Protein Domain Requirements for HOXA13:MEIS Interaction
    Developmental biology, 2005
    Co-Authors: Thomas M. Williams, Melissa E. Williams, Jeffrey W. Innis
    Abstract:

    AbdB-like HOX proteins form DNA-binding complexes with the TALE superclass proteins MEIS1A and MEIS1B, and trimeric complexes have been identified in nuclear extracts that include a second TALE protein, PBX. Thus, soluble DNA-independent protein-protein complexes exist in mammals. The extent of HOX/TALE superclass interactions, protein structural requirements, and sites of in vivo cooperative interaction have not been fully explored. We show that HOXA13 and Hoxd13 expression does not overlap with that of Meis1-3 in the developing limb; however, coexpression occurs in the developing male and female reproductive tracts (FRTs). We demonstrate that both HOXA13 and HOXD13 associate with MEIS1B in mammalian and yeast cells, and that HOXA13 can interact with all MEIS proteins but not more diverged TALE superclass members. In addition, the C-terminal domains (CTDs) of MEIS1A (18 amino acids) and MEIS1B (93 amino acids) are necessary for HOXA13 interaction; for MEIS1B, this domain was also sufficient. We also show by yeast two-hybrid assay that MEIS proteins can interact with anterior HOX proteins, but for some, additional N-terminal MEIS sequences are required for interaction. Using deletion mutants of HOXA13 and HOXD13, we provide evidence for multiple HOX peptide domains interacting with MEIS proteins. These data suggest that HOX:MEIS interactions may extend to non-AbdB-like HOX proteins in solution and that differences may exist in the MEIS peptide domains utilized by different HOX groups. Finally, the capability of multiple HOX domains to interact with MEIS C-terminal sequences implies greater complexity of the HOX:MEIS protein-protein interactions and a larger role for variation of HOX amino-terminal sequences in specificity of function.

  • range of hox tale superclass associations and protein domain requirements for HOXA13 meis interaction
    Developmental Biology, 2005
    Co-Authors: Thomas M. Williams, Melissa E. Williams, Jeffrey W. Innis
    Abstract:

    AbdB-like HOX proteins form DNA-binding complexes with the TALE superclass proteins MEIS1A and MEIS1B, and trimeric complexes have been identified in nuclear extracts that include a second TALE protein, PBX. Thus, soluble DNA-independent protein-protein complexes exist in mammals. The extent of HOX/TALE superclass interactions, protein structural requirements, and sites of in vivo cooperative interaction have not been fully explored. We show that HOXA13 and Hoxd13 expression does not overlap with that of Meis1-3 in the developing limb; however, coexpression occurs in the developing male and female reproductive tracts (FRTs). We demonstrate that both HOXA13 and HOXD13 associate with MEIS1B in mammalian and yeast cells, and that HOXA13 can interact with all MEIS proteins but not more diverged TALE superclass members. In addition, the C-terminal domains (CTDs) of MEIS1A (18 amino acids) and MEIS1B (93 amino acids) are necessary for HOXA13 interaction; for MEIS1B, this domain was also sufficient. We also show by yeast two-hybrid assay that MEIS proteins can interact with anterior HOX proteins, but for some, additional N-terminal MEIS sequences are required for interaction. Using deletion mutants of HOXA13 and HOXD13, we provide evidence for multiple HOX peptide domains interacting with MEIS proteins. These data suggest that HOX:MEIS interactions may extend to non-AbdB-like HOX proteins in solution and that differences may exist in the MEIS peptide domains utilized by different HOX groups. Finally, the capability of multiple HOX domains to interact with MEIS C-terminal sequences implies greater complexity of the HOX:MEIS protein-protein interactions and a larger role for variation of HOX amino-terminal sequences in specificity of function.

  • Genomes & Developmental Control Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability
    2005
    Co-Authors: Thomas M. Williams, Melissa E. Williams, Rork Kuick, David E. Misek, Kevin T. Mcdonagh, Samir M. Hanash, Jeffrey W. Innis
    Abstract:

    Hox genes encode transcription factors that regulate the morphogenesis of developing embryos. In mammals, knowledge of the genetic pathways, including the possible direct or indirect targets, regulated by HOX proteins is extremely limited. To identify the downstream genes regulated by posterior HOX proteins, we expressed HOXA13 in mouse embryonic fibroblasts lacking paralog group 13 expression using a bicistronic HOXA13/EGFP retroviral vector. Microarray analysis identified 68 genes with significant, reproducible RNA expression changes (50 activated; 18 repressed) in stable HOXA13-expressing cells. Genes with the GO annotation terms bextracellular matrixQ and bbasement membraneQ were greatly overrepresented, and several were shown to be regulated by HOX proteins in other studies. Among the genes strongly activated by HOXA13 were Enpp2, a bifunctional enzyme known to modulate tumor and normal cell motility and which is expressed in precartilaginous condensations; Fhl1, a transcription factor implicated in muscle cell differentiation and development; and M32486, a putative integral membrane molecule expressed in the female reproductive tract. Expression differences in the HOXA13expressing cells were confirmed for selected downstream genes using semi-quantitative RT-PCR, and in vivo coexpression with HOXA13 in the limb interdigital mesenchyme was demonstrated for many. For two candidates, Igfbp4 and Fstl, interdigital limb bud expression was reduced in HOXA13 mutants. To explore whether paralogous and nonparalogous HOX proteins could regulate the same genes, we created new HOX cell lines and examined the expression of selected genes identified by the HOXA13 screen. HOXD13 similarly activated/repressed 6 tested candidates, demonstrating that multiple downstream genetic pathways may be regulated by paralog HOX proteins. In contrast, HOXA9 was only able to repress expression of some gene targets. A HOXD13 mutant, HOXD13 IQN N AAA , incapable of monomeric DNAbinding, activated the expression of 5 HOXA13-upregulated genes; but was incapable of repressing the expression of Ngef and Casp8ap2. Our results suggest that HOX protein–protein interactions without direct HOX DNA-binding may play a larger role in HOX transcriptional regulation than generally assumed, and DNA-binding appears critical for repression.

J. C. Zenteno - One of the best experts on this subject based on the ideXlab platform.

  • mutational analysis of hoxd13 and HOXA13 genes in the triphalangeal thumb brachyectrodactyly syndrome
    Journal of Orthopaedic Research, 2002
    Co-Authors: A Perezcabrera, Susana Kofmanalfaro, J. C. Zenteno
    Abstract:

    Abstract The triphalangeal thumb–brachyectrodactyly syndrome is a very rare autosomal dominant disorder of unknown etiology characterized by an unusual pattern of limb malformations: triphalangeal thumbs and brachyectrodactyly in the hands, and ectrodactyly in the feet. In a previous report, we described the clinical and radiographical features of three related subjects with the disease and suggest that due to the unusual combination of limb defects and to its phenotypic similarity with the limb malformative pattern induced by disrupting the Hoxd13 gene in mouse, the triphalangeal thumb–brachyectrodactyly syndrome might be caused by mutations in a HOX gene. After sequencing the entire coding region of HOXD13 and the highly conserved homeodomain encoding region of HOXA13, we do not detect any deleterious mutation in any of the patients excluding that alterations at these sequences are responsible for the disease. Mutations in regulatory regions of these genes or in other genes involved in limb development might be responsible for the disease.

  • Mutational analysis of HOXD13 and HOXA13 genes in the triphalangeal thumb–brachyectrodactyly syndrome
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2002
    Co-Authors: A. Pérez-cabrera, Susana Kofman-alfaro, J. C. Zenteno
    Abstract:

    Abstract The triphalangeal thumb–brachyectrodactyly syndrome is a very rare autosomal dominant disorder of unknown etiology characterized by an unusual pattern of limb malformations: triphalangeal thumbs and brachyectrodactyly in the hands, and ectrodactyly in the feet. In a previous report, we described the clinical and radiographical features of three related subjects with the disease and suggest that due to the unusual combination of limb defects and to its phenotypic similarity with the limb malformative pattern induced by disrupting the Hoxd13 gene in mouse, the triphalangeal thumb–brachyectrodactyly syndrome might be caused by mutations in a HOX gene. After sequencing the entire coding region of HOXD13 and the highly conserved homeodomain encoding region of HOXA13, we do not detect any deleterious mutation in any of the patients excluding that alterations at these sequences are responsible for the disease. Mutations in regulatory regions of these genes or in other genes involved in limb development might be responsible for the disease.

H. Scott Stadler - One of the best experts on this subject based on the ideXlab platform.

  • The formation of the thumb requires direct modulation of Gli3 transcription by HOXA13.
    Proceedings of the National Academy of Sciences of the United States of America, 2020
    Co-Authors: Maria Felix Bastida, Susan Mackem, Anna Trofka, Rushikesh Sheth, H. Scott Stadler, Rocío Pérez-gómez, Jianjian Zhu, Alvaro Rada-iglesias, Marian A Ros
    Abstract:

    In the tetrapod limb, the digits (fingers or toes) are the elements most subject to morphological diversification in response to functional adaptations. However, despite their functional importance, the mechanisms controlling digit morphology remain poorly understood. Here we have focused on understanding the special morphology of the thumb (digit 1), the acquisition of which was an important adaptation of the human hand. To this end, we have studied the limbs of the HOXA13 mouse mutant that specifically fail to form digit 1. We show that, consistent with the role of HOXA13 in Hoxd transcriptional regulation, the expression of Hoxd13 in HOXA13 mutant limbs does not extend into the presumptive digit 1 territory, which is therefore devoid of distal Hox transcripts, a circumstance that can explain its agenesis. The loss of Hoxd13 expression, exclusively in digit 1 territory, correlates with increased Gli3 repressor activity, a Hoxd negative regulator, resulting from increased Gli3 transcription that, in turn, is due to the release from the negative modulation exerted by Hox13 paralogs on Gli3 regulatory sequences. Our results indicate that HOXA13 acts hierarchically to initiate the formation of digit 1 by reducing Gli3 transcription and by enabling expansion of the 5′Hoxd second expression phase, thereby establishing anterior−posterior asymmetry in the handplate. Our work uncovers a mutual antagonism between Gli3 and Hox13 paralogs that has important implications for Hox and Gli3 gene regulation in the context of development and evolution.

  • Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13.
    Cell reports, 2016
    Co-Authors: Rushikesh Sheth, H. Scott Stadler, Iros Barozzi, David Langlais, Marco Osterwalder, Stephen Nemec, Hanqian L. Carlson, Axel Visel, Jacques Drouin, Marie Kmita
    Abstract:

    The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in HOXA13-/-; Hoxd13-/- limbs. Our results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules.

  • HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia.
    Developmental dynamics : an official publication of the American Association of Anatomists, 2007
    Co-Authors: Carley Shaut, Chie Saneyoshi, Emily Morgan, Wendy M. Knosp, Diane R. Sexton, H. Scott Stadler
    Abstract:

    Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because HOXA13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis-regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7.

  • Elucidation, quantitative refinement, and in vivo utilization of the HOXA13 DNA binding site.
    The Journal of biological chemistry, 2007
    Co-Authors: Wendy M. Knosp, Chie Saneyoshi, Hans Peter Bächinger, Siming Shou, H. Scott Stadler
    Abstract:

    Mutations in HOXA13 cause malformations of the appendicular skeleton and genitourinary tract, including digit loss, syndactyly, and hypospadias. To determine the molecular basis for these defects, the DNA sequences bound by HOXA13 were empirically determined, revealing a novel high affinity binding site. Correlating the utilization of this high affinity binding site with genes exhibiting perturbed expression in HOXA13 mutant limbs, we identified that HOXA13 suppresses the expression of the BMP antagonist, Sostdc1. In the absence of HOXA13 function, Sostdc1 is ectopically expressed in the distal limb, causing reduced expression of BMP-activated genes and decreased SMAD phosphorylation. Limb chromatin immunoprecipitation revealed HOXA13 binding at its high affinity site in two conserved Sostdc1 regulatory sites in vivo. In vitro, HOXA13 represses gene expression through the Sostdc1 high affinity binding sites in a dosage-dependent manner. Together, these findings confirm that the high affinity HOXA13 binding site deduced by quantitative analyses is used in vivo to facilitate HOXA13 target gene regulation, providing a critical advance toward understanding the molecular basis for defects associated with the loss of HOXA13 function.

  • Genitourinary functions of HOXA13 and Hoxd13.
    Journal of biochemistry, 2005
    Co-Authors: Virginia Scott, Emily Morgan, H. Scott Stadler
    Abstract:

    In the United States, Japan, United Kingdom, and Sweden, birth defects affecting the growth and development of the genitourinary (GU) regions are becoming increasingly prevalent, with incidences ranging as high as 1 in 125 live births. To understand the basis for these malformations, scientists have begun to examine the function of developmental genes in GU tissues. At the forefront of these investigations are studies examining the role of the 5' HOX proteins during the formation of the GU region. In this report we discuss what is known about HOXA13 and HOXD13 function during GU development, highlighting some of the cellular and molecular mechanisms controlled by these proteins during the GU formation. Finally, the translational benefits of identifying HOX target genes are discussed; first to explain the prevalence of some GU defects as well as a mechanism to facilitate their prevention in the birth population.

Ke-neng Chen - One of the best experts on this subject based on the ideXlab platform.

  • downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy
    Thoracic Cancer, 2018
    Co-Authors: Qi Shi, Wanpu Yan, Lu-yan Shen, Bin Dong, Xiaozheng Kang, Liang Dai, Yongbo Yang, Ke-neng Chen
    Abstract:

    BACKGROUND Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. METHODS One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half-maximal inhibitory concentration of cisplatin, apoptosis, and epithelial-to-mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit-8, flow cytometry, and transwell analysis. RESULTS The median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half-maximal inhibitory concentration of cisplatin (P < 0.05), increased cisplatin-induced apoptosis (P < 0.05), and decreased EMT (P < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase-3 and cleaved PARP expression induced by cisplatin increased, while expression of E-cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells. CONCLUSION High HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin-resistance and promoted EMT in ESCC cells.

  • Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy
    Thoracic cancer, 2018
    Co-Authors: Qi Shi, Wanpu Yan, Lu-yan Shen, Bin Dong, Xiaozheng Kang, Liang Dai, Yongbo Yang, Ke-neng Chen
    Abstract:

    BACKGROUND Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. METHODS One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half-maximal inhibitory concentration of cisplatin, apoptosis, and epithelial-to-mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit-8, flow cytometry, and transwell analysis. RESULTS The median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half-maximal inhibitory concentration of cisplatin (P 

  • Exploration of target genes of HOXA13 in esophageal squamous cell carcinoma cell line.
    Cancer letters, 2011
    Co-Authors: Lu-yan Shen, Ke-neng Chen
    Abstract:

    Homeobox genes encode transcriptional factors which regulate cell proliferation and differentiation and have been found to be deregulated in many tumors. Previously, we found that the median survival time of patients with ESCC (Esophageal squamous cell carcinoma) expressing HOXA13 was significantly shorter than those with HOXA13-negative ESCC and we also demonstrated that knockdown of HOXA13 blocked cell proliferation in vitro and in vivo. In this study, we examined the protein expression changes after HOXA13 knockdown by 2-dimentional electrophoresis. Forty-five spots were significantly different, among which 24 were down-regulated and 21 were up-regulated after HOXA13 knockdown. The proteins from 14 gel-spots were further characterized by MALDI-TOF MS, among which, AnnexinA2, MnSOD and ERAB, are validated by Western Blot analysis. Transcriptional target analysis revealed that HOXA13 regulated several cell signaling pathways that are critically involved in cell proliferation, survival and migration. These results provide an additional support to a hypothesis that HOXA13 might participate in the carcinogenesis of ESCC.

  • HOXA13 Promotes Cancer Cell Growth and Predicts Poor Survival of Patients with Esophageal Squamous Cell Carcinoma
    Cancer research, 2009
    Co-Authors: Lu-yan Shen, Hua Wang, Xiao-mei Chen, Tao Ning, Ke-neng Chen
    Abstract:

    Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. Here, we investigated whether inhibition of HOXA13, a member of the homeobox genes, was sufficient to affect the proliferation of esophageal cancer cells in vitro and in vivo, and studied the association between HOXA13 expression and survival of patients with esophageal squamous cell carcinoma (ESCC). HOXA13 expression was permanently knocked down using an RNA interference technique, and cell strain with stable knockdown of HOXA13 protein was established. Colony formation assay showed that the number of colonies in HOXA13 protein-deficient cells was significantly less than that of control cells (P < 0.01). Tumor growth in nude mice showed that the weight and volume of tumors from the HOXA13 knockdown cells was significantly less than that from the control cells (P < 0.01). Then, HOXA13 expression in ESCC specimens and paired noncancerous mucosa was detected by immunohistochemistry, and overexpression of HOXA13 was found to be more pronounced in ESCCs than paired noncancerous mucosa (P < 0.05). Furthermore, the association of HOXA13 expression and disease-free survival time was analyzed in 155 ESCC cases. The median survival time of patients expressing HOXA13 was significantly shorter than HOXA13-negative patients (P = 0.0006). Multivariate analysis indicated that tumor-node-metastasis (TNM) stage and HOXA13 expression were independent predictors of disease-free survival time of patients with ESCC. Our results showed that HOXA13 expression enhanced tumor growth in vitro and in vivo, and was a negative independent predictor of disease-free survival of patients with ESCC.

  • Up-regulation of HOXA13 in esophageal squamous cell carcinoma of stage IIa and its effect on the prognosis
    Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery, 2009
    Co-Authors: Wanpu Yan, Lu-yan Shen, Ke-neng Chen
    Abstract:

    Objective To investigate the expression of HOXA13 gene in stage-Ⅱa esophageal squamous cell carcinoma(ESCC), and to evaluate its relationship with clinicopathological characteristics and prognosis. Methods The expression of HOXAI3 was examined by immunohistochemistry(IHC) in specimens from 39 patients with ESCC of stage-Ⅱa, who underwent resection from 1995 to 2002. SPSS software was used to analyze the relationship between HOXA13 expression and clinicopathological characteristics and prognosis of patients. Results The expression of HOXA13 protein was detected in ESCC tissue, and the positive rate was 61.5%. The median survival time of patients without HOXA13 expression(>72 months) was significanfly longer than those with HOXA13 expression (24 months)(P=0.023). Multivariate analysis showed that HOXA13 expression was independent predictor of disease-free survival time of patients with ESCC. Conclusion The expression of HOXA13 can be detected in ESCC and is a negative independent predictor of disease-free survival, which implies that HOXA13 might play a role in ESSC, and may be used as a clinical tumor marker of ESCC. Key words: Esophageal squamous cell carcinoma;  Gene, HOXA13;  Multivariate analysis;  Prognosis

D Garciacruz - One of the best experts on this subject based on the ideXlab platform.

  • split hand malformation hypospadias microphthalmia distinctive face and short stature in two brothers suggest a new syndrome
    American Journal of Medical Genetics Part A, 2005
    Co-Authors: Jose E Garciaortiz, Felipe Bandaespinoza, Juan C Zenteno, Luz M Galvanuriarte, Pablo Ruizflores, D Garciacruz
    Abstract:

    Split hand/foot malformation (SHFM) is a genetically heterogeneous limb malformation that may be isolated or associated with other malformations. More than 50 recognizable entities with SHFM have been described and at least 5 mapped genetic loci have been implicated. Two brothers with intrauterine growth retardation, short stature, distinctive face, microphthalmia, genital anomalies, and SHFM are described. Molecular analyses of TP63, HOXA13, and HOXD13 genes were normal. We propose this pattern to be a newly recognized SHFM syndrome. © 2005 Wiley-Liss, Inc.