title: High level of messenger RNA for BRMS1 in primary breast carcinomas is associated with poor prognosis.
abstract: BRMS1 is regarded as a metastasis suppressor gene for its ability to reduce metastatic potential of human and murine breast cancer cells as well as human melanoma cells. However, BRMS1 association to human tumor progression is not clearly understood. In the present study we analyzed BRMS1 mRNA expression in tumor progression and its potential prognostic value for breast carcinoma. BRMS1 mRNA expression level was quantified by real-time PCR in 47 tumoral, in 14 peritumoral and in 15 metastatic microdissected cellular populations from 47 breast cancer patients with 10-year follow up. We found BRMS1 expression to be higher in carcinoma cells than in matching normal epithelial cell populations in 10 out of 14 cases (p = 0.0005), while lymph-nodal carcinoma cells showed lower BRMS1 expression in 9 out of 15 cases (p = 0.001). Using both in vivo (human mammary breast carcinomas) and in vitro systems (breast cancer cell lines) we were able to demonstrate that BRMS1 overexpression was not a bias effect induced by cell proliferation rate. BRMS1 expression levels did not correlate with standard breast cancer prognostic factors but BRMS1 higher expression was associated with patient shorter disease-free and overall survival. Our findings are apparently inconsistent with the concept of BRMS1 as a metastasis suppressor gene. One possible explanation is that epithelial cells increase their BRMS1 expression as a compensatory response to tumor formation or metastasis progression, which is elevated in proportion to tumor aggressiveness, whereas those cells of the primary tumor that cannot upregulate BRMS1 escape to form metastasis.
authors.affiliation: Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Via Roma 57, 56126 Pisa, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Capodanno
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Iorio
authors.forename: Paolo
authors.initials: P
authors.lastname: Aretini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Isola
authors.forename: Mariella
authors.initials: M
authors.lastname: Tancredi
authors.forename: Paola
authors.initials: P
authors.lastname: Collecchi
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.forename: Romana Prosperi
authors.initials: RP
authors.lastname: Porta
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Caligo
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000556:secondary; D004848:Epithelium / Q000473:pathology; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured
chemical_list: C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins