title: BAG-1 expression correlates with Bcl-2, p53, differentiation, estrogen and progesterone receptors in invasive breast carcinoma.
abstract: BAG-1, a recently identified anti-apoptotic protein, is overexpressed in the majority of invasive breast carcinomas. Overexpression of BAG-1 is important for both multi-step oncogenesis and resistance of cancer cells to apoptosis induced by DNA-damaging alkylating agents. BAG-1 protein species are localized differentially; nuclear expression may be associated with a shorter disease-free and overall survival in early stage breast cancer, while cytoplasmic expression has been associated with longer survival in non-small cell lung cancer. Growing evidence suggests that Bcl-2 and p53 are also involved in the oncogenesis of breast cancer. Since BAG-1 interacts with Bcl-2 and is upregulated by mutant p53 in vitro, it would be interesting to determine if their expressions are correlated with each other and with other clinical prognostic factors in invasive breast cancer. To address this question we conducted a large scale retrospective study of BAG-1, Bcl-2 and p53 in 185 breast cancer patients. Our study again showed that BAG-1 is overexpressed in the majority of breast cancer patients. In addition, it demonstrated that the expression of BAG-1 correlates with that of Bcl-2, p53, differentiation, estrogen and progesterone receptors. Our clinical study supports the preclinical finding of the interaction between BAG-1 and Bcl-2, p53 and estrogen and progesterone receptors. Further experiments to explore the prognostic and therapeutic role of BAG-1 in breast cancer are warranted.
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA. stang@med.miami.edu
authors.forename: Shou-Ching
authors.initials: SC
authors.lastname: Tang
authors.forename: Jessalyn
authors.initials: J
authors.lastname: Beck
authors.forename: Sean
authors.initials: S
authors.lastname: Murphy
authors.forename: Garry
authors.initials: G
authors.lastname: Chernenko
authors.forename: Desmond
authors.initials: D
authors.lastname: Robb
authors.forename: Peter
authors.initials: P
authors.lastname: Watson
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Khalifa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D016923:Cell Death; D002454:Cell Differentiation; D004249:DNA Damage; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies; D016019:Survival Analysis; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53