The Role of a LIM Only Factor, LMO-4, in Breast Cancer
Annual rept. 18 Sep 2001-17 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. Yet, LMO-4 is not induced by estrogen, suggesting that it may participate in an estrogen-independent pathway. 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 lobuloalveolar 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.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research