Hedgehog pathway activity in the LADY prostate tumor model
Open Access
- 7 March 2007
- journal article
- Published by Springer Science and Business Media LLC in Molecular Cancer
- Vol. 6 (1), 19
- https://doi.org/10.1186/1476-4598-6-19
Abstract
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.Keywords
This publication has 21 references indexed in Scilit:
- Hedgehog Signaling in the ProstateJournal of Urology, 2007
- Sonic hedgehog-patched Gli signaling in the developing rat prostate gland: lobe-specific suppression by neonatal estrogens reduces ductal growth and branchingDevelopmental Biology, 2004
- Hedgehog signalling in prostate regeneration, neoplasia and metastasisNature, 2004
- Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signalingProceedings of the National Academy of Sciences of the United States of America, 2004
- Hedgehog Signaling Promotes Prostate Xenograft Tumor GrowthEndocrinology, 2004
- Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesisDevelopmental Biology, 2004
- Sonic hedgehog regulates prostatic growth and epithelial differentiationDevelopmental Biology, 2003
- Inhibition of Epithelial Ductal Branching in the Prostate by Sonic Hedgehog Is Indirectly Mediated by Stromal CellsPublished by Elsevier BV ,2003
- Hedgehog signaling in animal development: paradigms and principlesGenes & Development, 2001
- Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.1998