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

  • Visvader J
  • Venter D
  • Hahm K
 et al. 
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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.

Author-supplied keywords

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

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  • J E Visvader

  • D Venter

  • K Hahm

  • M Santamaria

  • E Y Sum

  • L O'Reilly

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