Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
LIMD1 is a member of the ZYXIN family of related proteins which includes AJUBA, TRIP6, LPP, WTIP, migfilin, and ZYXIN. The LIMD1 locus, 3p21.3, has been shown to undergo loss of heterozygosity in neoplastic tissues, suggesting potential tumor suppressor function. To further understand the role of LIMD1 in cancer, we have characterized endogenous expression of the LIMD1 protein and evaluated LIMD1 RNA expression in primary human breast tumors. LIMD1 levels were found to be constant throughout the cell cycle, but LIMD1 is phosphorylated during mitosis in HeLa cells. In addition, we observed colocalization of endogenous LIMD1 with vinculin at focal adhesions. In the MDA-MB435 cell line, which lacks LIMD1 expression, we detected methylation of the putative promoter region. LIMD1 mRNA expression was found to vary among primary human breast tumors; however, differences in LIMD1 expression in human breast cancers were not associated with DNA methylation of the predicted promoter region. These results suggest that some breast tumors have altered expression of LIMD1 RNA and that LIMD1 may be involved in cell anchoring via focal adhesions and in the cell cycle, particularly during mitosis.
Huggins
Christopher Jack
CJ
Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ont., Canada M5G 1X5.
Andrulis
Irene L
IL
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D060588:LIM Domain Proteins; D008938:Mitosis; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C403807:LIMD1 protein, human; D012313:RNA