Functional Analysis of LIM Domain Proteins and Co-Factors in Breast Cancer
Annual summary rept. 17 Sep 2002-16 Sep 2003
CALIFORNIA UNIV IRVINE
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We 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 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 ductal development in virgin mice and alveolar development of pregnant mice, indicating that LMOA 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, and identified several cancer-related genes that are regulated by LMO4. In addition, we have shown that LMO4 interacts with the transcription factor GATA3 in breast cancer cells. We propose that LMO4 is involved in regulation of breast cancer cells by interacting with GATA3.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research