Journal
ONCOGENE
Volume 26, Issue 46, Pages 6619-6629Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210487
Keywords
androgen receptor; estrogen receptor; receptor antagonist; Src; xenografts
Funding
- Intramural NIH HHS Funding Source: Medline
Ask authors/readers for more resources
In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor ( EGF) trigger association of the androgen receptor ( AR)- estradiol receptor ( ER) (alpha or beta) complex with Src. This interaction activates Src and affects the G1 to S cell cycle progression. In this report, we identify the sequence responsible for the AR/ Src interaction and describe a 10 amino- acid peptide that inhibits this interaction. Treatment of the human prostate or mammary cancer cells ( LNCaP or MCF- 7, respectively) with nanomolar concentrations of this peptide inhibits the androgen- or estradiol- induced association between the AR or the ER and Src the Src/ Erk pathway activation, cyclin D1 expression and DNA synthesis, without interfering in the receptor- dependent transcriptional activity. Similarly, the peptide prevents the S phase entry of LNCaP and MCF- 7 cells treated with EGF as well as mouse embryo fibroblasts stimulated with androgen or EGF. Interestingly, the peptide does not inhibit the S phase entry and cytoskeletal changes induced by EGF or serum treatment of AR- negative prostate cancer cell lines. The peptide is the first example of a specific inhibitor of steroid receptor-dependent signal transducing activity. The importance of these results is highlighted by the finding that the peptide strongly inhibits the growth of LNCaP xenografts established in nude mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available