The LIM Domain Gene LM04 Inhibits Differentiation of Mammary Epithelial Cells in vitro and is Overexpressed in Breast Cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 25; pp. 14452 - 14457
• Main Authors: Visvader, Jane E., Venter, Deon, Hahm, Kyungmin, Santamaria, Margaret, Eleanor Y. M. Sum, O'Reilly, Lorraine, White, David, Williams, Rachael, Armes, Jane, Lindeman, Geoffrey J.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 04.12.2001
• Subjects: Biological Sciences; Breast cancer; Breasts; Cell lines; Epithelial cells; Genes; Mammary glands; Oncogenes; RNA; T lymphocytes; Tumors
• ISSN: 0027-8424

LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have explored a role for LMO4, initially described as a human breast tumor autoantigen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy. Consistent with a role in proliferation, forced expression of this gene inhibited differentiation of mammary epithelial cells. Overexpression of LM04 mRNA was observed in 5 of 10 human breast cancer cell lines. Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LM04 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LM04 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.