GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
TableEdit
PMID:16489008
You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki
See Help for Help on this wiki. See the documentation for how to use the table editor
| Citation |
Adolphe, C, Hetherington, R, Ellis, T and Wainwright, B (2006) Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res. 66:2081-8 |
|---|---|
| Abstract |
Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of beta-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G1-S phase and G2-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a "gatekeeper." In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors. |
| Links |
PubMed Online version:10.1158/0008-5472.CAN-05-2146 |
| Keywords |
Animals; Carcinoma, Basal Cell/genetics; Carcinoma, Basal Cell/metabolism; Carcinoma, Basal Cell/pathology; Cell Cycle/physiology; Cell Nucleus/metabolism; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology; Cyclin B/metabolism; Cyclin B1; Cyclin D1/metabolism; Hair Follicle/metabolism; Hair Follicle/pathology; Mice; Mice, Transgenic; Receptors, Cell Surface/biosynthesis; Receptors, Cell Surface/genetics; Receptors, Cell Surface/physiology; Receptors, Notch/metabolism; Skin/metabolism; Skin/pathology; Skin Neoplasms/genetics; Skin Neoplasms/metabolism; Skin Neoplasms/pathology; beta Catenin/metabolism |
| public |
| Cancel |
