Cellular expression, localization and interactions of the product of the human MOST-1 gene associated with breast and prostate cancers.
We previously isolated and characterized the novel human gene MOST-1 (C8orf17) that is ubiquitously expressed in all cancer cell lines tested but differentially expressed in normal adult tissues. MOST-1 maps to chromosome region 8q24.2 whose amplification is frequently associated with breast and prostate cancers. RT-PCR analyses of breast and prostatic biopsies revealed MOST-1 overexpression and/or amplification in high-grade carcinomas. We raised and characterized a polyclonal antibody against a MOST-1-specific synthetic peptide. in vitro expression of MOST-1 protein revealed a tendency to exist as high molecular mass isoforms which are SDS-insoluble upon thermal stress. MOST-1 displayed cytoplasmic localization in four human cell lines (hTERT-HME1 normal mammary epithelial, MCF7 breast adenocarcinoma, PrEC normal prostate epithelial and DU145 prostate carcinoma), with polar expression during cell division. Knockdown of MOST-1 expression in DU145 cells resulted in reduced cell proliferation but enhanced apoptosis implying a putative mitogenic role of MOST-1. Yeast two-hybrid analyses demonstrated interaction with seven human proteins, most of which are overexpressed in tumors or involved in metabolic pathways. The interacting proteins were creatine kinase, Gardner feline sarcoma v-FGR oncogene product, telethonin, SNC73 protein, ferritin light chain, peripheral benzodiazepine receptor, and immunoglobulin C (mu) and C (delta) heavy chain. Co-immunoprecipitation assays validated the interactions of MOST-1 with the latter three proteins. Our results suggest that MOST-1 is associated with cell survival, proliferation and progression of cancer cells.
Tan
Jeanne M M
JM
Human Genome Laboratory, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
Chow
Vincent T K
VT
D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C516613:C8orf17 protein, human; D009363:Neoplasm Proteins