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Functional Analysis of LIM Domain Proteins and Co-Factors in Breast Cancer
Annual summary rept. 17 Sep 2001-16 Sep 2002
CALIFORNIA UNIV IRVINE
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We recently identified a novel transcription factor, LMO-4, which exhibits prominent expression in epithelial cells, including that of the breast. Since previous members of the LIM only LMO gene family are oncogenes in lymphocytes, we hypothesized that LMO-4 may play a role in mammary gland development and cancer. We have now shown that expression of LMO-4 is associated with undifferentiated cellular stage of breast epithelial cells, such as that found during lobuloalveolar development in pregnancy and in breast cancer. We have created transgenic mice in which we overexpress a dominant negative LMO-4 under the MMTV promoter MMTV- engrailed-LMO4 to test the role of LMO-4 in mammary gland development. Our results show significant inhibition of tobuloalveolar development in these MMTV-engrailed-LMO4 transgenic mice, indicating that LMO-4 plays roles in proliferation andor invasion of breast epithelial cells. Because these cellular features are associated with breast carcinogenesis and because LMO-4 is overexpressed in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene in breast cancer. We have also created stable breast cancer cell lines in which we can induce expression of LMO4 and Clim2, thus allowing us in future work to identify interacting proteins and study the role of these genes on breast cancer cell proliferation.
APPROVED FOR PUBLIC RELEASE