The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform

G Gremel - One of the best experts on this subject based on the ideXlab platform.

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British Journal of Cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, I Murphy, L Unwin, C Joyce, W Faller
    Abstract:

    Background: The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Methods: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro . For TMA construction, tumour material from 218 melanoma patients was used. Results: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival ( P =0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. Conclusions: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British journal of cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, L Unwin, C Joyce, Ian G. Murphy, William J. Faller
    Abstract:

    The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

B K Vonderhaar - One of the best experts on this subject based on the ideXlab platform.

  • Progesterone receptor activates MSX2 expression by downregulating TNAP/Akp2 and activating the Bmp pathway in EpH4 mouse mammary epithelial cells.
    PloS one, 2012
    Co-Authors: Jodie M. Fleming, A S Goldhar, Erika Ginsburg, Joshua J. Plant, B K Vonderhaar
    Abstract:

    Previously we demonstrated that EpH4 mouse mammary epithelial cells induced the homeobox Transcription Factor MSX2 either when transfected with the progesterone receptor (PR) or when treated with Bmp2/4. MSX2 upregulation was unaffected by Wnt inhibitors s-FRP or Dkk1, but was inhibited by the Bmp antagonist Noggin. We therefore hypothesized that PR signaling to MSX2 acts through the Bmp receptor pathway. Herein, we confirm that transcripts for Alk2/ActR1A, a non-canonical BmpR Type I, are upregulated in mammary epithelial cells overexpressing PR (EpH4-PR). Increased phosphorylation of Smads 1,5, 8, known substrates for Alk2 and other BmpR Type I proteins, was observed as was their translocation to the nucleus in EpH4-PR cells. Analysis also showed that Tissue Non-Specific Alkaline Phosphatase (TNAP/Akp2) was also found to be downregulated in EpH4-PR cells. When an Akp2 promoter-reporter construct containing a ½PRE site was transfected into EpH4-PR cells, its expression was downregulated. Moreover, siRNA mediated knockdown of Akp2 increased both Alk2 and MSX2 expression. Collectively these data suggest that PR inhibition of Akp2 results in increased Alk2 activity, increased phosphorylation of Smads 1,5,8, and ultimately upregulation of MSX2. These studies imply that re-activation of the Akp2 gene could be helpful in downregulating aberrant MSX2 expression in PR+ breast cancers.

  • Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of MSX2
    Oncogene, 2007
    Co-Authors: K Satoh, R C Hovey, T Malewski, A Warri, A S Goldhar, E Ginsburg, K Saito, J P Lydon, B K Vonderhaar
    Abstract:

    Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing Transcription Factor, MSX2, during branching morphogenesis is suggested from its ontogenic expression profile and hormonal regulation. Herein, we define the spatio-temporal control of MSX2 expression, the regulation of its expression by P and its direct role in ductal branching morphogenesis. P induces MSX2 in the presence of estrogen (E) both in vitro and in vivo while absence of the P receptor (PR) decreased MSX2 expression. Stable transfection of PR into mouse mammary epithelial cells increased the endogenous expression of MSX2 and their ability to undergo branching morphogenesis in vitro . Furthermore, normal mammary cells stably-transfected with MSX2 demonstrated increased branching morphogenesis in vitro while transgenic mice expressing MSX2 in their mammary glands demonstrated enhanced lateral branching during early development. The action of P on branching morphogenesis appears to involve Bmp2/4. Together, these data demonstrate that P, acting through PR-A and the Bmp2/4 pathway, induces MSX2 to enhance ductal branching in the mammary glands.

William J. Faller - One of the best experts on this subject based on the ideXlab platform.

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British journal of cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, L Unwin, C Joyce, Ian G. Murphy, William J. Faller
    Abstract:

    The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

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

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British Journal of Cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, I Murphy, L Unwin, C Joyce, W Faller
    Abstract:

    Background: The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Methods: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro . For TMA construction, tumour material from 218 melanoma patients was used. Results: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival ( P =0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. Conclusions: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

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

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British Journal of Cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, I Murphy, L Unwin, C Joyce, W Faller
    Abstract:

    Background: The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Methods: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro . For TMA construction, tumour material from 218 melanoma patients was used. Results: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival ( P =0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. Conclusions: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

  • Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
    British journal of cancer, 2011
    Co-Authors: G Gremel, D Ryan, M Rafferty, F Lanigan, S Hegarty, M Lavelle, L Unwin, C Joyce, Ian G. Murphy, William J. Faller
    Abstract:

    The homeobox containing Transcription Factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.