Dysregulation of normal programmed cell death mechanisms plays an important role in the pathogenesis and progression of breast cancer, as well as in responses of tumors to therapeutic intervention. Overexpression of anti-apoptotic members of the Bcl-2 family such as Bcl-2 and Bcl-X(L) has been implicated in cancer chemoresistance, whereas high levels of pro-apoptotic proteins such as Bax promote apoptosis and sensitize tumor cells to various anticancer therapies. Though the mechanisms by which Bcl-2 family proteins regulate apoptosis are diverse, ultimately they govern decision steps that determine whether certain caspase family cell death proteases remain quiescent or become active. To date, approximately 17 cellular homologs of Bcl-2 and at least 15 caspases have been identified in mammals. Other types of proteins may also modulate apoptotic responses through effects on apoptosis-regulatory proteins, such as BAG-1-a heat shock protein 70 kDa (Hsp70/Hsc70)-binding protein that can modulate stress responses and alter the functions of a variety of proteins involved in cell death and division. In this report, we summarize our attempts thus far to explore the expression of several Bcl-2 family proteins, caspase-3, and BAG-1 in primary breast cancer specimens and breast cancer cell lines. Moreover, we describe some of our preliminary observations concerning the prognostic significance of these apoptosis regulatory proteins in breast cancer patients, contrasting results derived from women with localized disease (with or without node involvement) and metastatic cancer.

This article has been cited by other articles:

				C. R. Loehberg, T. Thompson, M. B. Kastan, K. H. Maclean, D. G. Edwards, F. S. Kittrell, D. Medina, O. M. Conneely, and B. W. O'Malley Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis Cancer Res., December 15, 2007; 67(24): 12026 - 12033. [Abstract] [Full Text] [PDF]

				V Malamou-Mitsi, H Gogas, U Dafni, A Bourli, T Fillipidis, M Sotiropoulou, D Vlachodimitropoulos, S Papadopoulos, O Tzaida, G Kafiri, et al. Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy Ann. Onc., October 1, 2006; 17(10): 1504 - 1511. [Abstract] [Full Text] [PDF]

				F. Vegran, R. Boidot, C. Oudin, J.-M. Riedinger, F. Bonnetain, and S. Lizard-Nacol Overexpression of caspase-3s splice variant in locally advanced breast carcinoma is associated with poor response to neoadjuvant chemotherapy. Clin. Cancer Res., October 1, 2006; 12(19): 5794 - 5800. [Abstract] [Full Text] [PDF]

				A. Y. Savinov, A. G. Remacle, V. S. Golubkov, M. Krajewska, S. Kennedy, M. J. Duffy, D. V. Rozanov, S. Krajewski, and A. Y. Strongin Matrix Metalloproteinase 26 Proteolysis of the NH2-Terminal Domain of the Estrogen Receptor {beta} Correlates with the Survival of Breast Cancer Patients. Cancer Res., March 1, 2006; 66(5): 2716 - 2724. [Abstract] [Full Text] [PDF]

				M. Milella, D. Trisciuoglio, T. Bruno, L. Ciuffreda, M. Mottolese, A. Cianciulli, F. Cognetti, U. Zangemeister-Wittke, D. Del Bufalo, and G. Zupi Trastuzumab Down-Regulates Bcl-2 Expression and Potentiates Apoptosis Induction by Bcl-2/Bcl-XL Bispecific Antisense Oligonucleotides in HER-2Gene-Amplified Breast Cancer Cells Clin. Cancer Res., November 15, 2004; 10(22): 7747 - 7756. [Abstract] [Full Text] [PDF]

				L. Yang, Z. Cao, H. Yan, and W. C. Wood Coexistence of High Levels of Apoptotic Signaling and Inhibitor of Apoptosis Proteins in Human Tumor Cells: Implication for Cancer Specific Therapy Cancer Res., October 15, 2003; 63(20): 6815 - 6824. [Abstract] [Full Text] [PDF]

				M. Hensel, A. Schneeweiss, H.-P. Sinn, G. Egerer, M. Kornacker, E. Solomayer, R. Haas, G. Bastert, and A. D. Ho Stem Cell Dose and Tumorbiologic Parameters as Prognostic Markers for Patients with Metastatic Breast Cancer Undergoing High-Dose Chemotherapy with Autologous Blood Stem Cell Support Stem Cells, January 1, 2002; 20(1): 32 - 40. [Abstract] [Full Text] [PDF]

				R. I. Cutress, P. A. Townsend, A. C. Bateman, P.W.M. Johnson, K. Ryder, D. M. Barnes, G. Packham, B. C. Turner, and J. C. Reed BAG-1 Immunostaining and Survival in Early Breast Cancer J. Clin. Oncol., August 15, 2001; 19(16): 3706 - 3707. [Abstract] [Full Text] [PDF]

				M. Parton, M. Dowsett, and I. Smith Studies of apoptosis in breast cancer BMJ, June 23, 2001; 322(7301): 1528 - 1532. [Full Text] [PDF]