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Hedgehog pathway activity in the LADY prostate tumor model

BACKGROUND: Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate ca...

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Detalles Bibliográficos
Autores principales: Gipp, Jerry, Gu, Guangyu, Crylen, Curtis, Kasper, Susan, Bushman, Wade
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820793/
https://www.ncbi.nlm.nih.gov/pubmed/17343742
http://dx.doi.org/10.1186/1476-4598-6-19
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author Gipp, Jerry
Gu, Guangyu
Crylen, Curtis
Kasper, Susan
Bushman, Wade
author_facet Gipp, Jerry
Gu, Guangyu
Crylen, Curtis
Kasper, Susan
Bushman, Wade
author_sort Gipp, Jerry
collection PubMed
description BACKGROUND: Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined. RESULTS: We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin. CONCLUSION: Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.
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spelling pubmed-18207932007-03-13 Hedgehog pathway activity in the LADY prostate tumor model Gipp, Jerry Gu, Guangyu Crylen, Curtis Kasper, Susan Bushman, Wade Mol Cancer Research BACKGROUND: Robust Hedgehog (Hh) signaling has been implicated as a common feature of human prostate cancer and an important stimulus of tumor growth. The role of Hh signaling has been studied in several xenograft tumor models, however, the role of Hh in tumor development in a transgenic prostate cancer model has never been examined. RESULTS: We analyzed expression of Hh pathway components and conserved Hh target genes along with progenitor cell markers and selected markers of epithelial differentiation during tumor development in the LADY transgenic mouse model. Tumor development was associated with a selective increase in Ihh expression. In contrast Shh expression was decreased. Expression of the Hh target Patched (Ptc) was significantly decreased while Gli1 expression was not significantly altered. A survey of other relevant genes revealed significant increases in expression of Notch-1 and Nestin together with decreased expression of HNF3a/FoxA1, NPDC-1 and probasin. CONCLUSION: Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development. BioMed Central 2007-03-07 /pmc/articles/PMC1820793/ /pubmed/17343742 http://dx.doi.org/10.1186/1476-4598-6-19 Text en Copyright © 2007 Gipp et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Gipp, Jerry
Gu, Guangyu
Crylen, Curtis
Kasper, Susan
Bushman, Wade
Hedgehog pathway activity in the LADY prostate tumor model
title Hedgehog pathway activity in the LADY prostate tumor model
title_full Hedgehog pathway activity in the LADY prostate tumor model
title_fullStr Hedgehog pathway activity in the LADY prostate tumor model
title_full_unstemmed Hedgehog pathway activity in the LADY prostate tumor model
title_short Hedgehog pathway activity in the LADY prostate tumor model
title_sort hedgehog pathway activity in the lady prostate tumor model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820793/
https://www.ncbi.nlm.nih.gov/pubmed/17343742
http://dx.doi.org/10.1186/1476-4598-6-19
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