Human MUC1 Oncoprotein is of Functional Importance to the Development of Prostate Cancer
Annual rept. 1 Mar 2008-28 Feb 2009
DANA-FARBER CANCER INST BOSTON MA
Pagination or Media Count:
The MUC1 oncoprotein is overexpressed in prostate cancers with aggressive clinicopathologic features and is associated with an elevated risk of recurrence. Our hypothesis is that MUC1 is of functional importance to the development of aggressive prostate cancer and that this effect is mediated through interaction with the androgen receptor AR. The Specific Aims of this Idea Award are 1 To define the interaction between MUC1 and AR in vitro and in prostate cancer cells 2 To assess the effects of MUC1 on AR-mediated gene expression and 3 To define the effects of MUC1 on growth and survival of prostate cancer cells in response to androgen stimulation and treatment with antiandrogens. Work supported by the first year of this Award has demonstrated that the MUC1-C receptor constitutively associates with AR in androgen-unresponsive prostate cancer cells. The MUC1-C cytoplasmic domain MUC1-CD binds directly to the AR DNA binding domain. Specific sequences in MUC1-CD that confer the interaction have been identified and used to identify drugs that block binding to AR. One lead agent has been found to induce death of androgen-unresponsive, and not -responsive, prostate cancer cells. These findings, based on the results of MUC1-CD binding to AR, should provide the basis for the design of new agents to treat androgen-unresponsive prostate cancer.
- Medicine and Medical Research