Characterization of Breast Cancer Susceptibility Gene BRCA2
Abstract
Estrogen promotes proliferation in the MCF-7 breast cancer cell line via high levels of estrogen receptor. The primary mode of estrogen action has been considered to be through the transcriptional activation of gene containing estrogen response elements including the immediate early genes c-myc and fos. Recent reports have indicated that estrogen is capable of activating the MAPK cytoplasmic signaling cascade. In this study, specific small molecule inhibitors of MAPK (PD098059) and P13-K (LY294002) activity were used to determine the influence of these cascades on estrogen-mediated mitogenesis. Both compounds decreased the fraction of cells entering DNA synthesis after treatment with l7 Beta-estradiol. While a small decrease was noted in estrogen stimulated transcriptional activity, these drugs did not inhibit expression of myc or fos. However, both drugs did prevent the accumulation of cyclin Dl, cdk2 activation, and hyperphosphorylation of the retinoblastoma protein indicating that the block occurred at, or prior to, this point in the cell cycle. Interestingly, the downstream targets of these kinase cascades, Erk1, Erk2, and PKB, were not activated over basal levels in response to estrogen treatment. These studies indicate that estrogen initiates mitogenesis by inducing the transcription of immediate early genes, but cytoplasmic signaling pathways play an important role in the control of subsequent events in the cell cycle.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADB257340
Entities
People
- Edward Lobenhofer
- Jeff Marks
Organizations
- Duke University Hospital