The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer.
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.
Visvader
J E
JE
The Walter and Eliza Hall Institute of Medical Research and Bone Marrow Research Laboratories, Melbourne, Victoria 3050, Australia. visvader@wehi.edu.au
Venter
D
D
Hahm
K
K
Santamaria
M
M
Sum
E Y
EY
O'Reilly
L
L
White
D
D
Williams
R
R
Armes
J
J
Lindeman
G J
GJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002364:Caseins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002364:Caseins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486312:LDB1 protein, human; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; C102084:Ldb1 protein, mouse; C491976:Lmo4 protein, mouse; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors