Multiple forms of BRMS1 are differentially expressed in the MCF10 isogenic breast cancer progression model.
Clinical studies evaluating the mRNA expression level of the BRMS1 metastasis suppressor in the progression of breast cancer have not been consistent. The purpose of this study was to characterize endogenous BRMS1 mRNA and protein in a model of the progression of breast cancer. BRMS1 protein expression was evaluated in the genetically related MCF10 cell lines representing 'normal' breast epithelial cells (MCF10A), pre-malignant breast disease (MCF10AT), comedo ductal carcinoma in situ (MCF10DCIS.com), and metastatic carcinoma (MCF10CAa.1 and MCF10CAd.1alpha) with two antibodies that recognize distinct epitopes in the BRMS1 protein. Nuclear expression of the characteristic *35 kDa BRMS1 protein was detected in all cell lines. Because BRMS1 was expressed in the metastatic MCF10 variants, the BRMS1 exons were sequenced to scan for possible genetic mutations. BRMS1 was wild-type with the exception of a synonymous T/C transition in exon 7. However, alternatively spliced variants were detected by RT-PCR. Two variants, BRMS1.v2 and BRMS1.v4 were only detected in the MCF10A and AT cell lines, while BRMS1 and BRMS1.v3 were detected in all lines. These results demonstrate that expression of the characteristic *35 kDa BRMS1 protein is not sufficient to prevent metastasis. The differential expression of alternative splice variants suggests caution should be taken when evaluating BRMS1 mRNA in clinical samples.
Hurst
Douglas R
DR
Department of Pathology, University of Alabama at Birmingham, 1670 University Blvd., room VH-G019A, Birmingham, AL 35294-0019, USA. dhurst@uab.edu
Xie
Yi
Y
Edmonds
Mick D
MD
Welch
Danny R
DR
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D014183:Transplantation, Heterologous
C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins