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

J E Visvader; D Venter; K Hahm; M Santamaria; E Y Sum; L O'Reilly; D White; R Williams; J Armes; G J Lindeman

doi:10.1073/pnas.251547698

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

Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14452-7. doi: 10.1073/pnas.251547698.

Authors

J E Visvader¹, D Venter, K Hahm, M Santamaria, E Y Sum, L O'Reilly, D White, R Williams, J Armes, G J Lindeman

Affiliation

¹ The Walter and Eliza Hall Institute of Medical Research and Bone Marrow Research Laboratories, Melbourne, Victoria 3050, Australia. [email protected]

Abstract

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 LMO4 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 LMO4 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Caseins / biosynthesis
Cell Differentiation / genetics
DNA-Binding Proteins / genetics
Epithelial Cells / cytology
Epithelial Cells / metabolism
Female
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics*
Humans
In Situ Hybridization
LIM Domain Proteins
Mammary Glands, Animal / cytology*
Mammary Glands, Animal / growth & development
Mammary Glands, Animal / metabolism
Mice
Pregnancy
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
Transcription Factors / genetics*
Tumor Cells, Cultured

Substances

Adaptor Proteins, Signal Transducing
Caseins
DNA-Binding Proteins
Homeodomain Proteins
LDB1 protein, human
LIM Domain Proteins
LMO4 protein, human
Ldb1 protein, mouse
Lmo4 protein, mouse
RNA, Messenger
RNA, Neoplasm
Transcription Factors