Clinical Cancer Research, Vol 2, Issue 7 1215-1219, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells

R Kumar, M Mandal, A Lipton, H Harvey and CB Thompson
Departments of Medicine and Cellular, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

Overexpression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. Here we investigated the effects of HER2 on expression of apoptotic pathways and modulation of tamoxifen-induced apoptosis in ER-positive MCF-7 breast cancer cells. We report that HER2 overexpression in MCF-7 cells is accompanied by up-regulation of antiapoptotic Bcl-2 and Bcl-XL proteins and suppression of tamoxifen-induced apoptosis. In addition, human tumor cell lines that are both ER positive and overexpress HER2 also express enhanced levels of Bcl-2 compared to cells that are either ER positive or overexpress HER2 alone. Our findings suggest that possible deregulation of antiapoptotic Bcl-2 and Bcl-XL may be associated with the enhanced survival of HER2-overexpressing and ER-positive breast cancer cells treated with antiestrogens.

This article has been cited by other articles:

				N. C. Peterson, M. D. Servinsky, A. Christian, Z. Peng, W. Qiu, J. Mann, J. Dicello, and D. L. Huso Tamoxifen resistance and Her2/neu expression in an aged, irradiated rat breast carcinoma model Carcinogenesis, September 1, 2005; 26(9): 1542 - 1552. [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]

				Z. Yang, C. J. Barnes, and R. Kumar Human Epidermal Growth Factor Receptor 2 Status Modulates Subcellular Localization of and Interaction with Estrogen Receptor {alpha} in Breast Cancer Cells Clin. Cancer Res., June 1, 2004; 10(11): 3621 - 3628. [Abstract] [Full Text] [PDF]

				V. Benoit, A. Chariot, L. Delacroix, V. Deregowski, N. Jacobs, M.-P. Merville, and V. Bours Caspase-8-Dependent HER-2 Cleavage in Response to Tumor Necrosis Factor {alpha} Stimulation Is Counteracted by Nuclear Factor {kappa}B through c-FLIP-L Expression Cancer Res., April 15, 2004; 64(8): 2684 - 2691. [Abstract] [Full Text] [PDF]

				W. Tangkeangsirisin, J. Hayashi, and G. Serrero PC Cell-Derived Growth Factor Mediates Tamoxifen Resistance and Promotes Tumor Growth of Human Breast Cancer Cells Cancer Res., March 1, 2004; 64(5): 1737 - 1743. [Abstract] [Full Text] [PDF]

				A. H. Talukder, R. Bagheri-Yarmand, R. R. E. Williams, J. Ragoussis, R. Kumar, and A. Raz Antihuman Epidermal Growth Factor Receptor 2 Antibody Herceptin Inhibits Autocrine Motility Factor (AMF) Expression and Potentiates Antitumor Effects of AMF Inhibitors Clin. Cancer Res., October 1, 2002; 8(10): 3285 - 3289. [Abstract] [Full Text] [PDF]

				A. S. Knoop, S. M. Bentzen, M. M. Nielsen, B. B. Rasmussen, and C. Rose Value of Epidermal Growth Factor Receptor, HER2, p53, and Steroid Receptors in Predicting the Efficacy of Tamoxifen in High-Risk Postmenopausal Breast Cancer Patients J. Clin. Oncol., July 15, 2001; 19(14): 3376 - 3384. [Abstract] [Full Text] [PDF]

				R. C. Bast Jr, P. Ravdin, D. F. Hayes, S. Bates, H. Fritsche Jr, J. M. Jessup, N. Kemeny, G. Y. Locker, R. G. Mennel, and M. R. Somerfield 2000 Update of Recommendations for the Use of Tumor Markers in Breast and Colorectal Cancer: Clinical Practice Guidelines of the American Society of Clinical Oncology J. Clin. Oncol., March 15, 2001; 19(6): 1865 - 1878. [Abstract] [Full Text] [PDF]

				R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance Pharmacol. Rev., March 1, 2001; 53(1): 25 - 72. [Abstract] [Full Text] [PDF]

				X. Li, M. Marani, R. Mannucci, B. Kinsey, F. Andriani, I. Nicoletti, L. Denner, and M. Marcelli Overexpression of BCL-XL Underlies the Molecular Basis for Resistance to Staurosporine-induced Apoptosis in PC-3 Cells Cancer Res., February 1, 2001; 61(4): 1699 - 1706. [Abstract] [Full Text]

				H. Roh, J. Pippin, and J. A. Drebin Down-Regulation of HER2/neu Expression Induces Apoptosis in Human Cancer Cells That Overexpress HER2/neu Cancer Res., February 1, 2000; 60(3): 560 - 565. [Abstract] [Full Text]

				L. Dong, W. Wang, F. Wang, M. Stoner, J. C. Reed, M. Harigai, I. Samudio, M. P. Kladde, C. Vyhlidal, and S. Safe Mechanisms of Transcriptional Activation of bcl-2 Gene Expression by 17beta -Estradiol in Breast Cancer Cells J. Biol. Chem., November 5, 1999; 274(45): 32099 - 32107. [Abstract] [Full Text] [PDF]

				G.-J. Zhang, I. Kimijima, M. Onda, M. Kanno, H. Sato, T. Watanabe, A. Tsuchiya, R. Abe, and S. Takenoshita Tamoxifen-induced Apoptosis in Breast Cancer Cells Relates to Down-Regulation of bcl-2, but not bax and bcl-XL, without Alteration of p53 Protein Levels Clin. Cancer Res., October 1, 1999; 5(10): 2971 - 2977. [Abstract] [Full Text] [PDF]

				M. Mandal, S. B. Maggirwar, N. Sharma, S. H. Kaufmann, S.-C. Sun, and R. Kumar Bcl-2 Prevents CD95 (Fas/APO-1)-induced Degradation of Lamin B and Poly(ADP-ribose) Polymerase and Restores the NF-kappa B Signaling Pathway J. Biol. Chem., November 29, 1996; 271(48): 30354 - 30359. [Abstract] [Full Text] [PDF]

				R. Bagheri-Yarmand, R. K. Vadlamudi, R.-A. Wang, J. Mendelsohn, and R. Kumar Vascular Endothelial Growth Factor Up-regulation via p21-activated Kinase-1 Signaling Regulates Heregulin-beta 1-mediated Angiogenesis J. Biol. Chem., December 8, 2000; 275(50): 39451 - 39457. [Abstract] [Full Text] [PDF]

				A. H. Talukder, H. F. Jorgensen, M. Mandal, S. K. Mishra, R. K Vadlamudi, B. F. C. Clark, J. Mendelsohn, and R. Kumar Regulation of Elongation Factor-1alpha Expression by Growth Factors and Anti-receptor Blocking Antibodies J. Biol. Chem., February 16, 2001; 276(8): 5636 - 5642. [Abstract] [Full Text] [PDF]

				R. A. Campbell, P. Bhat-Nakshatri, N. M. Patel, D. Constantinidou, S. Ali, and H. Nakshatri Phosphatidylinositol 3-Kinase/AKT-mediated Activation of Estrogen Receptor alpha . A NEW MODEL FOR ANTI-ESTROGEN RESISTANCE J. Biol. Chem., March 23, 2001; 276(13): 9817 - 9824. [Abstract] [Full Text] [PDF]

				L.-H. Xu, X. Yang, C. A. Bradham, D. A. Brenner, A. S. Baldwin Jr., R. J. Craven, and W. G. Cance The Focal Adhesion Kinase Suppresses Transformation-associated, Anchorage-independent Apoptosis in Human Breast Cancer Cells. INVOLVEMENT OF DEATH RECEPTOR-RELATED SIGNALING PATHWAYS J. Biol. Chem., September 22, 2000; 275(39): 30597 - 30604. [Abstract] [Full Text] [PDF]