The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer

LM04 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have exp lored a role for LM04, initially described as a human breast tumor autoanti gen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expr essed predominantly in the lobuloalveoli of the mammary gland during pregna ncy. Consistent with a role in proliferation, forced expression of this gen e 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 r evealed overexpression of LM04 in 56% of specimens. immunohistochemistry co nfirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LM04 in maintaining proliferation of mammary epithelium an d suggest that deregulation of this gene may contribute to breast tumorigen esis.