title: BCAR1/p130Cas expression in untreated and acquired tamoxifen-resistant human breast carcinomas.
abstract: High BCAR1/p130Cas expression in primary breast tumour cytosol predicts a poor chance of response recurrent disease to tamoxifen treatment in patients with oestrogen receptor (ER)-positive breast carcinomas. In this study, we assessed whether BCAR1/p130Cas expression is altered during acquisition of anti-oestrogen resistance. BCAR1/p130Cas protein was quantitatively measured by chemiluminescent Western blot analysis in the cytosol of 34 predominantly ER(+) carcinomas that initially responded to primary tamoxifen treatment and subsequently progressed (n = 22 ) or developed during adjuvant tamoxifen treatment (n = 12) and compared to 54 untreated ER(+) human breast carcinomas. We did not detect significant differences in the level of BCAR1/p130Cas protein in untreated and acquired tamoxifen-resistant carcinomas. Our results indicate that in tumour progression towards tamoxifen resistance, increase of BCAR1/p130Cas may be only one of the molecular mechanisms. Thus, high BCAR1/p130Cas protein levels appear to be a hallmark for intrinsic resistance to tamoxifen in breast carcinomas.
authors.affiliation: Department of Pathology, Division of Molecular Biology, Josephine Nefkens Institute, University Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van der Flier
authors.forename: C M
authors.initials: CM
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Brinkman
authors.forename: M
authors.initials: M
authors.lastname: Smid
authors.forename: S R
authors.initials: SR
authors.lastname: Johnston
authors.forename: L C
authors.initials: LC
authors.lastname: Dorssers
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D050719:Crk-Associated Substrate Protein; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D011506:Proteins; D011960:Receptors, Estrogen / Q000032:analysis; D050717:Retinoblastoma-Like Protein p130; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D004965:Estrogen Antagonists; D010750:Phosphoproteins; D011506:Proteins; D011960:Receptors, Estrogen; D050717:Retinoblastoma-Like Protein p130; D013629:Tamoxifen