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The Role of a LIM Only Factor, LMO-4 in Breast Cancer

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Annual rept. 18 Sep 2002-17 Sep 2003

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LMO-4 is a transcription factor, 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. Furthermore, the ErbB2 activator heregulin stimulates LMO4 expression in MCF-7 breast cancer cells, suggesting that LMO4 plays a role in this important oncogenic pathway. In protein interactions studies, we have found that LMO4 interacts with DNA-binding proteins, including GATA3. 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 LMO4 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 LMO4 is overexpressed in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene in breast cancer.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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