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R. C. Coombes - One of the best experts on this subject based on the ideXlab platform.
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Keratin 19 mRNA is detectable by RT-PCR in lymph nodes of patients without breast cancer-reply
British Journal of Cancer, 1997Co-Authors: A. Schoenfeld, R. C. CoombesAbstract:Keratin 19 mRNA is detectable by RT-PCR in lymph nodes of patients without breast cancer-reply
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The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for Keratin 19
European Journal of Cancer, 1997Co-Authors: Andrew J. Schoenfeld, H D Sinnett, K.h. Kruger, J. J. Gomm, Jean-claude Gazet, N. Sacks, H.g. Bender, Y. Luqmani, R. C. CoombesAbstract:Abstract The aim of this study was to determine whether reverse transcriptase polymerase chain reaction (RT-PCR) for Keratin 19 (K19) provides additional information when combined with immunohisto-chemistry when used to detect micrometastases in blood and bone marrow in patients with primary breast cancer. We studied 78 patients with breast cancer who had no evidence of distant metastases. We collected blood and bone marrow, separated the mononuclear fraction and carried out RT-PCR and immunohistochemistry for K19. RT-PCR was done by two 40-cycle rounds using nested primers. In initial experiments, RT-PCR was shown to be capable of detecting one tumour cell in one million normal bone marrow cells, which was at least 10 times more sensitive than immunohistochemistry, while retaining specificity. Five per cent of the peripheral blood and 22% of the bone marrow samples contained K19 positive cells by immunohistochemistry staining. Using RT-PCR, these proportions increased to 25% and 35%, respectively. This represents a significantly greater detection frequency (P
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Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients.
British Journal of Cancer, 1996Co-Authors: A. Schoenfeld, Y. A. Luqmani, H D Sinnett, Sami Shousha, R. C. CoombesAbstract:We have used polymerase chain reaction (PCR) to measure Keratin 19 mRNA in order to detect breast cancer cells invading axillary lymph nodes. In a consecutive series of 125 patients with primary breast cancer, 75 patients had no evidence of lymph node involvement by conventional histology. A total of 530 lymph nodes from these patients were examined and 106 (20%) gave a Keratin 19 product detectable by Southern hybridisation. This correlated with primary tumour size (P
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Keratin 19 mrna measurement to detect micrometastases in lymph nodes in breast cancer patients
British Journal of Cancer, 1996Co-Authors: A. Schoenfeld, Y. A. Luqmani, H D Sinnett, Sami Shousha, R. C. CoombesAbstract:We have used polymerase chain reaction (PCR) to measure Keratin 19 mRNA in order to detect breast cancer cells invading axillary lymph nodes. In a consecutive series of 125 patients with primary breast cancer, 75 patients had no evidence of lymph node involvement by conventional histology. A total of 530 lymph nodes from these patients were examined and 106 (20%) gave a Keratin 19 product detectable by Southern hybridisation. This correlated with primary tumour size (P<0.001). These 106 nodes came from 23 patients. Thus, using this technique, 23/75 (30.6%) patients were found to have evidence of lymph node involvement who would otherwise have been designated lymph node negative.
Hiroki Koyama - One of the best experts on this subject based on the ideXlab platform.
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Histologic characteristics of breast cancers with occult lymph node metastases detected by Keratin 19 mRNA reverse transcriptase‐polymerase chain reaction
Cancer, 1996Co-Authors: Shinzaburo Noguchi, Tomohiko Aihara, Shingi Imaoka, Kazuyoshi Motomura, Hideo Inaji, Hiroki KoyamaAbstract:BACKGROUND Amplification of Keratin 19 mRNA (K19) by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a sensitive method to detect occult breast cancer metastases in lymph nodes. METHODS Axillary lymph nodes were obtained from 126 patients with breast cancer, and metastases in these lymph nodes were studied by both histologic examination and K19 RT-PCR. The patients were categorized into 3 groups according to the results of these 2 examinations, i.e., patients with 1) both histologically and K19 RT-PCR negative lymph nodes (metastases negative group [n = 91]); 2) histologically negative but K19 RT-PCR positive lymph nodes (occult metastases positive group [ n = 15]); and 3) histologically positive lymph nodes (metastases positive group [n = 20]). RESULTS Various histologic parameters such as tumor size, histologic type, histologic grade, lymphatic invasion, vascular invasion, and estrogen receptor status were compared among these three groups. There were no significant differences among any of these histologic parameters between the metastases positive and occult metastases positive groups. Conversely, tumor size of the metastases positive (2.5 +/- 0.2 cm) and occult metastases positive (2.5 +/- 0.2 cm) groups was significantly (P < 0.05) greater than that of the metastases negative group (1.9 +/- 0.1 cm), and positivity of lymphatic vessel invasion in the former 2 groups (70% and 53%, respectively) was also significantly (P < 0.01) greater than that in the latter group (18%). CONCLUSIONS These results demonstrate that histologic characteristics of breast cancers with occult metastases are similar to those of breast cancers with histologically detectable metastases.
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Detection of Gastric Cancer Micrometastases in Lymph Nodes by Amplification of Keratin 19 mRNA with Reverse Transcriptase‐Polymerase Chain Reaction
Japanese Journal of Cancer Research, 1996Co-Authors: Sbinzaburo Noguchi, Masahiro Hiratsuka, Hiroshi Furukawa, Tomohiko Aihara, Tsutomu Kasugai, Sumihito Tamura, Shingi Imaoka, Hiroki Koyama, Takeshi IwanagaAbstract:A sensitive method for the detection of gastric cancer micrometastases in lymph nodes was developed. The method was based on amplification of Keratin 19 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Keratin 19 RT-PCR showed that Keratin 19 mRNA was expressed in all 12 gastric cancers, but not in any of 20 normal control lymph nodes, indicating that Keratin 19 mRNA is a good target of RT-PCR for the detection of gastric cancer micrometastases in lymph nodes. Serial dilution studies of RNA extracted from gastric cancers against RNA extracted from control lymph nodes demonstrated that the detection sensitivity of the Keratin 19 RT-PCR method was one cancer cell in 10 3 -10 5 lymph node cells. Detectability of lymph node metastases was compared between Keratin 19 RT-PCR and conventional histological examination, using 100 lymph nodes obtained from 12 gastric cancer patients. Keratin 19 mRNA was detected in all of the seven lymph nodes which were histologically metastasis-positive. Of the 93 lymph nodes which were histologically metastasis-negative, 79 were found not to express Keratin 19 mRNA but 14 were found to express Keratin 19 mRNA, indicating that these lymph nodes contained micrometastases which could not be detected by histological examination. These results demonstrate that Keratin 19 RT-PCR is a more sensitive method than histological examination for the detection of gastric micrometastases in lymph nodes.
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detection of gastric cancer micrometastases in lymph nodes by amplification of Keratin 19 mrna with reverse transcriptase polymerase chain reaction
Japanese Journal of Cancer Research, 1996Co-Authors: Sbinzaburo Noguchi, Masahiro Hiratsuka, Hiroshi Furukawa, Tomohiko Aihara, Tsutomu Kasugai, Sumihito Tamura, Shingi Imaoka, Hiroki Koyama, Takeshi IwanagaAbstract:A sensitive method for the detection of gastric cancer micrometastases in lymph nodes was developed. The method was based on amplification of Keratin 19 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Keratin 19 RT-PCR showed that Keratin 19 mRNA was expressed in all 12 gastric cancers, but not in any of 20 normal control lymph nodes, indicating that Keratin 19 mRNA is a good target of RT-PCR for the detection of gastric cancer micrometastases in lymph nodes. Serial dilution studies of RNA extracted from gastric cancers against RNA extracted from control lymph nodes demonstrated that the detection sensitivity of the Keratin 19 RT-PCR method was one cancer cell in 10 3 -10 5 lymph node cells. Detectability of lymph node metastases was compared between Keratin 19 RT-PCR and conventional histological examination, using 100 lymph nodes obtained from 12 gastric cancer patients. Keratin 19 mRNA was detected in all of the seven lymph nodes which were histologically metastasis-positive. Of the 93 lymph nodes which were histologically metastasis-negative, 79 were found not to express Keratin 19 mRNA but 14 were found to express Keratin 19 mRNA, indicating that these lymph nodes contained micrometastases which could not be detected by histological examination. These results demonstrate that Keratin 19 RT-PCR is a more sensitive method than histological examination for the detection of gastric micrometastases in lymph nodes.
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Detection of breast cancer micrometastases in lymph nodes by amplification of Keratin 19 mRNA with reverse-transcriptase polymerase chain reaction
Gan to kagaku ryoho. Cancer & chemotherapy, 1996Co-Authors: Shinzaburo Noguchi, Tomohiko Aihara, Kazuyoshi Motomura, Hideo Inaji, Hiroki KoyamaAbstract:Keratin 19 mRNA reverse-transcriptase polymerase chain reaction (K 19 RT-PCR) was compared with histological examination in the detection of breast cancer micrometastases in axillary lymph nodes. Sixty-three axillary lymph nodes, which were obtained from 23 breast cancer patients, were bisected. One half was studied by conventional histological analysis of hematoxylin and eosin sections. Total RNA was extracted from the other half and subjected to K 19 RT-PCR. In all the ten lymph nodes, which were histologically metastasis-positive, K 19 mRNA was detected by RT-PCR. Of the 53 histologically negative lymph nodes, five (9%) lymph nodes were found to express K 19 mRNA, indicating the presence of micrometastases which could be detected by RT-PCR but not by a histological examination. These results demonstrate the usefulness of K 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes.
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Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and Keratin 19 mRNA amplification.
American Journal of Pathology, 1996Co-Authors: Shinzaburo Noguchi, Tomohiko Aihara, Shingi Imaoka, Kazuyoshi Motomura, Hideo Inaji, Hiroki KoyamaAbstract:Usefulness of MUC1 mRNA and Keratin 19 mRNA as a target of reverse-transcriptase polymerase chain reaction (RT-PCR) was compared in the detection of breast cancer micrometastases in axillary lymph nodes. RT-PCR amplification of MUC1 mRNA and Keratin 19 mRNA was conducted using total RNA samples. RT-PCR products were stained with ethidium bromide and analyzed by agarose gel electrophoresis. Expression of both MUC1 mRNA and Keratin 19 mRNA was detected by RT-PCR in a breast cancer cell line (MRK) and in all the 23 primary breast cancers but not in the control lymph nodes obtained from patients with benign diseases. A serial dilution study of MRK cells against normal lymph node cells has shown that detection sensitivity of MUC1 RT-PCR and Keratin 19 RT-PCR were 1/10(5) and 1/10(6) (cancer/lymph node cells), respectively. Sixty-three axillary lymph nodes were obtained from 23 patients with primary breast cancer, and metastases in each lymph node were investigated by histological examination (hematoxylin and eosin sections) and RT-PCR method. In all 10 lymph nodes, which were histologically metastasis-positive, both MUC1 mRNA and Keratin mRNA were detected by RT-PCR. Of the 53 histologically negative lymph nodes, 3 (6%) and 5 (9%) lymph nodes were found to express MUC1 mRNA and Keratin 19 mRNA, respectively, indicating the presence of micrometastases which could be detected by RT-PCR but not by histological examination. These results demonstrate the usefulness of both MUC1 RT-PCR and Keratin 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes, and also indicate the superiority of Keratin 19 RT-PCR over MUC1 RT-PCR because of its higher detection sensitivity.
Lucie Germain - One of the best experts on this subject based on the ideXlab platform.
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Identification of epithelial stem cells in vivo and in vitro using Keratin 19 and BrdU.
Methods of Molecular Biology, 2009Co-Authors: Danielle Larouche, Amélie Lavoie, Claudie Paquet, Carolyne Simard-bisson, Lucie GermainAbstract:Progress in the identification of skin stem cells and the improvement of culture methods open the possibility to use stem cells in regenerative medicine. Based on their quiescent nature, the development of label retention assays allowed the localization of skin stem cells in the bulge region of the pilosebaceous units and in the bottom of rete ridges in glabrous skin. The development of markers such as Keratin 19 also permits their study in human tissues. In this chapter, protocols to identify skin stem cells based on their slow-cycling property and their expression of Keratin 19 will be described in detail. The methods include the labeling of skin stem cells within mouse or rat tissues in vivo, the labeling of proliferative human cells in vitro using 5-bromo-2-deoxyuridine (BrdU), and the detection of Keratin 19 and BrdU by immunofluorescence or immunoperoxidase staining.
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Keratin 19 as a stem cell marker in vivo and in vitro.
Methods of Molecular Biology, 2005Co-Authors: Danielle Larouche, Cindy Jean Hayward, Kristine Cuffley, Lucie GermainAbstract:The skin is a dynamic tissue in which terminally differentiated Keratinocytes are replaced by the proliferation of new epithelial cells that will undergo differentiation. The rapid and continual turnover of skin throughout life depends on a cell population with unique characteristics: the stem cells. These cells are relatively undifferentiated, retain a high capacity for self-renewal throughout their lifetime, have a large proliferative potential, and are normally slow cycling. The long-term regeneration of grafted cultured epidermis indicates that epidermal stem cells are maintained in cultures. In animals they can be identified with 3H-thymidine or bromodeoxyuridine based on their property of slow cycling. The development of markers such as Keratin 19 also permits their study in human tissues. In this chapter, protocols to study skin stem cells using their property of slow cycling and their expression of Keratin 19 will be described in detail. The methods include the double labeling of tissues for Keratin 19 and label-retaining cells (auto radiography of 3H-thymidine) in situ. The labeling of Keratin 19 by immunofluorescence of by flow cytometry is described for cells in vitro.
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Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro Keratin 19 expressing cells are differentially localized in function of anatomic sites and their number varies with donor age and culture stage
Journal of Cell Science, 1996Co-Authors: Martine Michel, Marc Lussier, André Royal, Natalie Torok, Mariejosee Godbout, Pierrette Gaudreau, Lucie GermainAbstract:This study was undertaken to evaluate Keratin 19 (K19) as a biochemical marker for skin stem cells in order to address some long standing questions concerning these cells in the field of cutaneous biology. We first used the well-established mouse model enabling us to identify skin stem cells as [3H]thymidine-label-retaining cells. A site directed antibody was raised against a synthetic peptide of K19. It reacted specifically with a 40 kDa protein (K19) on immunoblotting. It labelled the bulge area of the outer root sheath on mouse skin by immunohistochemistry. Double-labelling revealed that K19-positive-cells were also [3H]thymidine-label-retaining cells, suggesting that K19 is a marker for skin stem cells of hair follicles. K19-expression was then used to investigate the variation in mouse and human skin stem cells as a function of body site, donor age and culture time. K19 was expressed in the hair follicle and absent from the interfollicular epidermis at hairy sites (except for some K18 coexpressing Merkel cells). In contrast, at glabrous sites, K19-positive-cells were in deep epidermal rete ridges. K19 expressing cells also contained high levels of alpha 3 beta 1 integrin. The proportion of K19-positive-cells was greater in newborn than older foreskins. This correlated with Keratinocyte culture lifespan variation with donor age. Moreover, it could explain clinical observations that children heal faster than adults. In conclusion, K19 expression in skin provides an additional tool to allow further characterization of skin stem cells under normal and pathological conditions in situ and in vitro.
Anil K. Rustgi - One of the best experts on this subject based on the ideXlab platform.
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The Pancreatic and Duodenal Homeobox Protein PDX-1 Regulates the Ductal Specific Keratin 19 through the Degradation of MEIS1 and DNA Binding
PLOS ONE, 2010Co-Authors: Johannes Von Burstin, Melanie P. Wescott, Maximilian Reichert, Anil K. RustgiAbstract:Background Pancreas organogenesis is the result of well-orchestrated and balanced activities of transcription factors. The homeobox transcription factor PDX-1 plays a crucial role in the development and function of the pancreas, both in the maintenance of progenitor cells and in determination and maintenance of differentiated endocrine cells. However, the activity of homeobox transcription factors requires coordination with co-factors, such as PBX and MEIS proteins. PBX and MEIS proteins belong to the family of three amino acid loop extension (TALE) homeodomain proteins. In a previous study we found that PDX-1 negatively regulates the transcriptional activity of the ductal specific Keratin 19 (Krt19). In this study, we investigate the role of different domains of PDX-1 and elucidate the functional interplay of PDX-1 and MEIS1 necessary for Krt19 regulation. Methodology/Principal Findings Here, we demonstrate that PDX-1 exerts a dual manner of regulation of Krt19 transcriptional activity. Deletion studies highlight that the NH2-terminus of PDX-1 is functionally relevant for the down-regulation of Krt19, as it is required for DNA binding of PDX-1 to the Krt19 promoter. Moreover, this effect occurs independently of PBX. Second, we provide insight on how PDX-1 regulates the Hox co-factor MEIS1 post-transcriptionally. We find specific binding of MEIS1 and MEIS2 to the Krt19 promoter using IP-EMSA, and siRNA mediated silencing of Meis1, but not Meis2, reduces transcriptional activation of Krt19 in primary pancreatic ductal cells. Over-expression of PDX-1 leads to a decreased level of MEIS1 protein, and this decrease is prevented by inhibition of the proteasome. Conclusions/Significance Taken together, our data provide evidence for a dual mechanism of how PDX-1 negatively regulates Krt19 ductal specific gene expression. These findings imply that transcription factors may efficiently regulate target gene expression through diverse, non-redundant mechanisms.
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The PDX1 Homeodomain Transcription Factor Negatively Regulates the Pancreatic Ductal Cell-specific Keratin 19 Promoter
Journal of Biological Chemistry, 2006Co-Authors: Therese B. Deramaudt, Mira M. Sachdeva, Melanie P. Wescott, Yuting Chen, Doris A. Stoffers, Anil K. RustgiAbstract:Keratin 19 is a member of the cytoKeratin family that is critical for maintenance of cellular architecture and organization, especially of epithelia. The pancreas has three distinct cell types, ductal, acinar, and islet, each with different functions. Embryologically, the pancreatic and duodenal homeobox 1 (PDX1) homeodomain protein is critical for the initiation of all pancreatic lineages; however, the later differentiation of the endocrine pancreas is uniquely dependent upon high PDX1 expression, whereas PDX1 is down-regulated in the ductal and acinar cell lineages. We find that this down-regulation may be required for normal ductal expression of cytoKeratin K19. The K19 promoter-reporter gene assay demonstrates that ectopic PDX1 inhibits K19 reporter gene activity in primary pancreatic ductal cells. This is reinforced by our findings that retrovirally mediated stable transduction of PDX1 in primary pancreatic ductal cells suppresses K19 expression, and short interfering RNA to PDX1 in Min6 insulinoma cells results in the induction of normally undetectable K19. Complementary functional and biochemical approaches led to the unexpected finding that a multimeric complex of PDX1 and two members of the TALE homeodomain factor family, MEIS1a and PBX1b, regulates K19 gene transcription through a specific cis-regulatory element (-341 to -325) upstream of the K19 transcription start site. These data suggest a unifying mechanism whereby PDX1, myeloid ecotropic viral insertion site (MEIS), and pre-B-cell leukemia transcription factor 1 (PBX) may regulate ductal and acinar lineage specification during pancreatic development. Specifically, concomitant PDX1 suppression and MEIS isoform expression result in proper ductal and acinar lineage specification. Furthermore, PDX1 may inhibit the ductal differentiation program in the pancreatic endocrine compartment, particularly beta cells.
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The Tissue-dependent Keratin 19 Gene Transcription Is Regulated by GKLF/KLF4 and Sp1
Journal of Biological Chemistry, 2000Co-Authors: Felix H. Brembeck, Anil K. RustgiAbstract:Keratins play critical roles in cellular differentiation and cytoskeletal organization. Keratin 19 (K19) is unique because it has been implicated as a marker of stem cells in some tissues, such as the hair follicle in the skin. It is also associated with malignant transformation in esophageal and pancreatic cancers. Here, we show that the K19 promoter is active in a subset of gastrointestinal cancer cells derived from esophageal and pancreas but inactive in other contexts. This activity was mapped to a short region containing an overlapping binding site for gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1. GKLF has a higher binding affinity and is the predominant binding factor in cells with low Sp-1 protein levels. Pancreatic acinar cells normally do not express K19, but overexpression of GKLF and Sp1 in these cells leads to aberrant expression, similar to what is observed in pancreatic cancer. These results demonstrate the functional interaction of ubiquitous and tissue-restricted transcription factors in determining tissue- and neoplasm-specific patterns of gene expression.
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the tissue dependent Keratin 19 gene transcription is regulated by gklf klf4 and sp1
Journal of Biological Chemistry, 2000Co-Authors: Felix H. Brembeck, Anil K. RustgiAbstract:Keratins play critical roles in cellular differentiation and cytoskeletal organization. Keratin 19 (K19) is unique because it has been implicated as a marker of stem cells in some tissues, such as the hair follicle in the skin. It is also associated with malignant transformation in esophageal and pancreatic cancers. Here, we show that the K19 promoter is active in a subset of gastrointestinal cancer cells derived from esophageal and pancreas but inactive in other contexts. This activity was mapped to a short region containing an overlapping binding site for gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1. GKLF has a higher binding affinity and is the predominant binding factor in cells with low Sp-1 protein levels. Pancreatic acinar cells normally do not express K19, but overexpression of GKLF and Sp1 in these cells leads to aberrant expression, similar to what is observed in pancreatic cancer. These results demonstrate the functional interaction of ubiquitous and tissue-restricted transcription factors in determining tissue- and neoplasm-specific patterns of gene expression.
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The Keratin 19 promoter is potent for cell-specific targeting of genes in transgenic mice.
Gastroenterology, 2000Co-Authors: Felix H. Brembeck, Jennifer Moffett, Timothy C. Wang, Anil K. RustgiAbstract:Abstract Background & Aims: Keratins are intermediate filaments that are critical in cytoskeletal organization. Their roles in cellular processes are underscored by inherited human diseases in which germline mutations of Keratins are found, as well as by transgenic and knockout mouse models that recapitulate those diseases. Keratin 19 (K19) has unique structural properties and developmental and spatial expression patterns. This suggests that K19 expression may correlate with important cell fate decisions in gastrointestinal tract epithelia. Methods: We used mouse K19 5' untranslated region and promoter sequences and fused it to the lacZ reporter gene in a transgene construct. Characterization was by β-galactosidase expression and X-gal histochemistry in gastrointestinal epithelia. Because endogenous K19 protein is transcriptionally regulated by the Kruppel-like transcription factor 4 (KLF4), we determined the spatial expression patterns of KLF4 and K19 in relationship to the lacZ reporter gene product. Results: K19-lacZ transgenic mice were found to have reporter gene expression in an epithelial-specific pattern. Expression was restricted to ductal epithelial cells in the pancreas, surface colonocytes, small intestinal villi, and gastric isthmus cells. Transgene expression correlated with K19 and KLF4 protein expression in the pancreas and stomach and was overlapping in the small and large intestine. Conclusions: The K19 promoter may be a useful tool to study epithelial cell biology and subsequent transdifferentiation programs, particularly the pancreas and stomach. GASTROENTEROLOGY 2001;120:1720-1728
Anastasia E. Konstantinidou - One of the best experts on this subject based on the ideXlab platform.
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Expression of caspase-14 and Keratin-19 in the human epidermis and appendages during fetal skin development
Archives of Dermatological Research, 2013Co-Authors: Ioannis D Gkegkes, George Agrogiannis, Efstratios Patsouris, Kyriaki Aroni, Anastasia E. KonstantinidouAbstract:Caspase-14 is a seemingly non-apoptotic caspase involved in Keratinocyte differentiation and cornification of the skin. Keratin-19 is an epithelial marker and a potential marker of epidermal stem cells that is expressed during human fetal skin development. We examined the immunohistochemical expression of caspase-14 in relation to CK-19 in the human fetal skin during development and perinatally, to assess their role in human skin maturation. Skin samples were received at autopsy. In the fetal epidermis, caspase-14 was predominantly expressed in the more differentiated layers, gradually disappearing from the basal layer toward term. By contrast, Keratin-19 expression gradually decreased with epidermal maturation through gestation (rho = −0.949; p = 0.0001) and was a marker of the germinative layers. Keratin-19 was preserved in scarce basal cell nests at term and postnatally. Caspase-14 and Keratin-19 were inversely expressed in the differentiating epidermal layers through gestation ( p
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expression of caspase 14 and Keratin 19 in the human epidermis and appendages during fetal skin development
Archives of Dermatological Research, 2013Co-Authors: Ioannis D Gkegkes, George Agrogiannis, Efstratios Patsouris, Kyriaki Aroni, Anastasia E. KonstantinidouAbstract:Caspase-14 is a seemingly non-apoptotic caspase involved in Keratinocyte differentiation and cornification of the skin. Keratin-19 is an epithelial marker and a potential marker of epidermal stem cells that is expressed during human fetal skin development. We examined the immunohistochemical expression of caspase-14 in relation to CK-19 in the human fetal skin during development and perinatally, to assess their role in human skin maturation. Skin samples were received at autopsy. In the fetal epidermis, caspase-14 was predominantly expressed in the more differentiated layers, gradually disappearing from the basal layer toward term. By contrast, Keratin-19 expression gradually decreased with epidermal maturation through gestation (rho = −0.949; p = 0.0001) and was a marker of the germinative layers. Keratin-19 was preserved in scarce basal cell nests at term and postnatally. Caspase-14 and Keratin-19 were inversely expressed in the differentiating epidermal layers through gestation (p < 0.0001). Concerning the appendages, in hair follicles and sebaceous glands, caspase-14 located preferentially in the more differentiated layers of the inner root sheath, whereas Keratin-19 was expressed in the outer sheath. Eccrine sweat glands showed a variable pattern of caspase-14 and Keratin-19 expression. In conclusion, caspase-14 emerged as a marker of human skin differentiation during development, while Keratin-19 marked the germinative epithelial layers in the fetal epidermis and appendages and possibly the nests of epidermal stem cells.
