LAF-4 is aberrantly expressed in human breast cancer.
LAF-4, which encodes a nuclear protein with transactivation potential, is fused to the MLL gene in acute lymphoblastic leukemia (ALL). We identified LAF-4 as a gene that is transcriptionally deregulated in breast tumors and thus may have a pathological role in mammary tumorigenesis. In line with the previous finding that LAF-4 expression is tissue specific, we did not detect any LAF-4 mRNA in normal mammary epithelial cell lines. However, 2 of 5 breast cancer cell lines were found to express LAF-4 at both the RNA and protein levels. In 2 of 9 primary tumor-normal pairs, the expression of LAF-4 was clearly elevated in the tumor tissue. Using RNA in situ hybridization, we demonstrated that LAF-4 is expressed in mammary tumor cells but not in normal acini. In a group of 64 primary human breast tumors, we found that LAF-4 was overexpressed in approximately 20% of the cases. Although epigenetic changes may be involved in altered expression of some genes, differences in LAF-4 expression were not associated with DNA methylation of the predicted promoter region. Our results suggest that LAF-4 may be a proto-oncogene that is transcriptionally activated in some cases of breast cancer.
To
Minh D
MD
Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Faseruk
Stephanie A
SA
Gokgoz
Nalan
N
Pinnaduwage
Dushanthi
D
Done
Susan J
SJ
Andrulis
Irene L
IL
D001940:Breast / Q000473:pathology / Q000503:physiopathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008593:Menopause; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C097738:AFF3 protein, human; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger