Abstract B71: Decreased expression of Tgfβ family members appears to be an acquired phenotype of progression to malignancy in the context of loss of Brca1 in mammary epithelial cells.

B71 Rational Loss of full length Brca1 in mammary epithelial cells of conditional knockout mice is associated with an aberrant proliferative response to estrogen treatment promoting cancer progression. We had previously found that loss of full-length Brca1 in mammary epithelial cells was associated with decreased expression of Tgfβ family members at early stage of malignancy. Initial time course study was conducted to find if decreased expression of growth inhibitory Tgfβ family members is directly related to loss of Brca1 in mammary epithelial cells. Methods Mammary gland tissue of Brca1f/f;MMTV-Cre and control wild-type mice from different time points: prior to puberty (age 2½ weeks), mid-puberty (age 6 weeks), end of puberty (age 10 weeks) and maturity (4 and 6 months) was isolated at the time of necropsy(N=3 per cohort). RNA expression levels of TGF-β 1,2,3 and TGF-βRI, II were measured by real time RT-PCR. Results No significant differences in the expression levels of Tgfβ family members between Brca1f/f;MMTV-Cre and wild-type mice were found at these time-points using current number of samples. Conclusions Decreased expression of Tgfβ family members in these mice does not seem to be directly associated with loss of Brca1 in mammary epithelial cells and appears to be an acquired phenotype as part of the malignancy progression, which would suggest that it is due to modulation of other signaling pathways. Funding: This study was supported by U.S. Army Medical Research and Material Command WX81XWH-07-1-0588(S. A. and P. A. F.) and Bridges to the Doctorate NIGMS 1R25GM075360-01(S. K. M.). Citation Information: Cancer Prev Res 2008;1(7 Suppl):B71.