This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zelinski, D. P. Articles by Kinch, M. S. Search for Related Content PubMed PubMed Citation Articles by Zelinski, D. P. Articles by Kinch, M. S.

EphA2 Overexpression Causes Tumorigenesis of Mammary Epithelial Cells¹

Departments of Basic Medical Sciences [D. P. Z., N. D. Z., J. C. S., M. S. K.] and Veterinary Pathobiology [A. R. I.], Purdue University, West Lafayette, Indiana 47907-1246

Elevated levels of protein tyrosine phosphorylation contribute to a malignant phenotype, although the tyrosine kinases that are responsible for this signaling remain largely unknown. Here we report increased levels of the EphA2 (ECK) protein tyrosine kinase in clinical specimens and cell models of breast cancer. We also show that EphA2 overexpression is sufficient to confer malignant transformation and tumorigenic potential on nontransformed (MCF-10A) mammary epithelial cells. The transforming capacity of EphA2 is related to the failure of EphA2 to interact with its cell-attached ligands. Interestingly, stimulation of EphA2 reverses the malignant growth and invasiveness of EphA2-transformed cells. Taken together, these results identify EphA2 as a powerful oncoprotein in breast cancer.

This article has been cited by other articles:

				J.-W. Lee, H. D. Han, M. M. K. Shahzad, S. W. Kim, L. S. Mangala, A. M. Nick, C. Lu, R. R. Langley, R. Schmandt, H.-S. Kim, et al. EphA2 Immunoconjugate as Molecularly Targeted Chemotherapy for Ovarian Carcinoma J Natl Cancer Inst, September 2, 2009; 101(17): 1193 - 1205. [Abstract] [Full Text] [PDF]

				S.-T. Chiu, K.-J. Chang, C.-H. Ting, H.-C. Shen, H. Li, and F.-J. Hsieh Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells Carcinogenesis, September 1, 2009; 30(9): 1475 - 1486. [Abstract] [Full Text] [PDF]

				M. Kawabe, M. Mandic, J. L. Taylor, C. A. Vasquez, A. K. Wesa, L. M. Neckers, and W. J. Storkus Heat Shock Protein 90 Inhibitor 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin Enhances EphA2+ Tumor Cell Recognition by Specific CD8+ T Cells Cancer Res., September 1, 2009; 69(17): 6995 - 7003. [Abstract] [Full Text] [PDF]

				B. Annamalai, X. Liu, U. Gopal, and J. S. Isaacs Hsp90 Is an Essential Regulator of EphA2 Receptor Stability and Signaling: Implications for Cancer Cell Migration and Metastasis Mol. Cancer Res., July 1, 2009; 7(7): 1021 - 1032. [Abstract] [Full Text] [PDF]

				J. M. Brannan, W. Dong, L. Prudkin, C. Behrens, R. Lotan, B. N. Bekele, I. Wistuba, and F. M. Johnson Expression of the Receptor Tyrosine Kinase EphA2 Is Increased in Smokers and Predicts Poor Survival in Non-Small Cell Lung Cancer Clin. Cancer Res., July 1, 2009; 15(13): 4423 - 4430. [Abstract] [Full Text] [PDF]

				D. Vaught, J. Chen, and D. M. Brantley-Sieders Regulation of Mammary Gland Branching Morphogenesis by EphA2 Receptor Tyrosine Kinase Mol. Biol. Cell, May 15, 2009; 20(10): 2572 - 2581. [Abstract] [Full Text] [PDF]

				M. L. Taddei, M. Parri, A. Angelucci, B. Onnis, F. Bianchini, E. Giannoni, G. Raugei, L. Calorini, N. Rucci, A. Teti, et al. Kinase-Dependent and -Independent Roles of EphA2 in the Regulation of Prostate Cancer Invasion and Metastasis Am. J. Pathol., April 1, 2009; 174(4): 1492 - 1503. [Abstract] [Full Text] [PDF]

				K. Miura, J.-M. Nam, C. Kojima, N. Mochizuki, and H. Sabe EphA2 Engages Git1 to Suppress Arf6 Activity Modulating Epithelial Cell-Cell Contacts Mol. Biol. Cell, April 1, 2009; 20(7): 1949 - 1959. [Abstract] [Full Text] [PDF]

				J. Wykosky and W. Debinski The EphA2 Receptor and EphrinA1 Ligand in Solid Tumors: Function and Therapeutic Targeting Mol. Cancer Res., December 1, 2008; 6(12): 1795 - 1806. [Abstract] [Full Text] [PDF]

				A. K. Wesa, C. J. Herrem, M. Mandic, J. L. Taylor, C. Vasquez, M. Kawabe, T. Tatsumi, M. S. Leibowitz, J. H. Finke, R. M. Bukowski, et al. Enhancement in Specific CD8+ T Cell Recognition of EphA2+ Tumors In Vitro and In Vivo after Treatment with Ligand Agonists J. Immunol., December 1, 2008; 181(11): 7721 - 7727. [Abstract] [Full Text] [PDF]

				D. Jackson, J. Gooya, S. Mao, K. Kinneer, L. Xu, M. Camara, C. Fazenbaker, R. Fleming, S. Swamynathan, D. Meyer, et al. A Human Antibody-Drug Conjugate Targeting EphA2 Inhibits Tumor Growth In vivo Cancer Res., November 15, 2008; 68(22): 9367 - 9374. [Abstract] [Full Text] [PDF]

				R. Buettner, T. Mesa, A. Vultur, F. Lee, and R. Jove Inhibition of Src Family Kinases with Dasatinib Blocks Migration and Invasion of Human Melanoma Cells Mol. Cancer Res., November 1, 2008; 6(11): 1766 - 1774. [Abstract] [Full Text] [PDF]

				M. Lackmann and A. W. Boyd Eph, a Protein Family Coming of Age: More Confusion, Insight, or Complexity? Sci. Signal., April 15, 2008; 1(15): re2 - re2. [Abstract] [Full Text] [PDF]

				W. B. Fang, R. C. Ireton, G. Zhuang, T. Takahashi, A. Reynolds, and J. Chen Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism J. Cell Sci., February 1, 2008; 121(3): 358 - 368. [Abstract] [Full Text] [PDF]

				J. Wykosky, D. M. Gibo, C. Stanton, and W. Debinski Interleukin-13 Receptor {alpha}2, EphA2, and Fos-Related Antigen 1 as Molecular Denominators of High-Grade Astrocytomas and Specific Targets for Combinatorial Therapy Clin. Cancer Res., January 1, 2008; 14(1): 199 - 208. [Abstract] [Full Text] [PDF]

				J. Wykosky, D. M. Gibo, and W. Debinski A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells Mol. Cancer Ther., December 1, 2007; 6(12): 3208 - 3218. [Abstract] [Full Text] [PDF]

				R Holm, S Knopp, Z Suo, C Trope, and J M Nesland Expression of EphA2 and EphrinA-1 in vulvar carcinomas and its relation to prognosis J. Clin. Pathol., October 1, 2007; 60(10): 1086 - 1091. [Abstract] [Full Text] [PDF]

				H. Nakanishi, T. Nakamura, E. Canaani, and C. M. Croce ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias PNAS, September 4, 2007; 104(36): 14442 - 14447. [Abstract] [Full Text] [PDF]

				M. Parri, F. Buricchi, E. Giannoni, G. Grimaldi, T. Mello, G. Raugei, G. Ramponi, and P. Chiarugi EphrinA1 Activates a Src/Focal Adhesion Kinase-mediated Motility Response Leading to Rho-dependent Actino/Myosin Contractility J. Biol. Chem., July 6, 2007; 282(27): 19619 - 19628. [Abstract] [Full Text] [PDF]

				N. K. Noren and E. B. Pasquale Paradoxes of the EphB4 Receptor in Cancer Cancer Res., May 1, 2007; 67(9): 3994 - 3997. [Abstract] [Full Text] [PDF]

				S. A. Hammond, R. Lutterbuese, S. Roff, P. Lutterbuese, B. Schlereth, E. Bruckheimer, M. S. Kinch, S. Coats, P. A. Baeuerle, P. Kufer, et al. Selective Targeting and Potent Control of Tumor Growth Using an EphA2/CD3-Bispecific Single-Chain Antibody Construct Cancer Res., April 15, 2007; 67(8): 3927 - 3935. [Abstract] [Full Text] [PDF]

				H.-J. Kim, B. C. Litzenburger, X. Cui, D. A. Delgado, B. C. Grabiner, X. Lin, M. T. Lewis, M. M. Gottardis, T. W. Wong, R. M. Attar, et al. Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail Mol. Cell. Biol., April 15, 2007; 27(8): 3165 - 3175. [Abstract] [Full Text] [PDF]

				A. B. Larsen, M. W. Pedersen, M.-T. Stockhausen, M. V. Grandal, B. v. Deurs, and H. S. Poulsen Activation of the EGFR Gene Target EphA2 Inhibits Epidermal Growth Factor-Induced Cancer Cell Motility Mol. Cancer Res., March 1, 2007; 5(3): 283 - 293. [Abstract] [Full Text] [PDF]

				F. Liu, P. J. Park, W. Lai, E. Maher, A. Chakravarti, L. Durso, X. Jiang, Y. Yu, A. Brosius, M. Thomas, et al. A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma Cancer Res., November 15, 2006; 66(22): 10815 - 10823. [Abstract] [Full Text] [PDF]

				C. N. Landen Jr., C. Lu, L. Y. Han, K. T. Coffman, E. Bruckheimer, J. Halder, L. S. Mangala, W. M. Merritt, Y. G. Lin, C. Gao, et al. Efficacy and Antivascular Effects of EphA2 Reduction With an Agonistic Antibody in Ovarian Cancer. J Natl Cancer Inst, November 1, 2006; 98(21): 1558 - 1570. [Abstract] [Full Text] [PDF]

				D. M. Brantley-Sieders, W. B. Fang, Y. Hwang, D. Hicks, and J. Chen Ephrin-A1 Facilitates Mammary Tumor Metastasis through an Angiogenesis-Dependent Mechanism Mediated by EphA Receptor and Vascular Endothelial Growth Factor in Mice Cancer Res., November 1, 2006; 66(21): 10315 - 10324. [Abstract] [Full Text] [PDF]

				K. Fukushima, Y. Ueno, J. Inoue, N. Kanno, and T. Shimosegawa Filopodia formation via a specific Eph family member and PI3K in immortalized cholangiocytes Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G812 - G819. [Abstract] [Full Text] [PDF]

				N.-Y. Yang, E. B. Pasquale, L. B. Owen, and I. M. Ethell The EphB4 Receptor-tyrosine Kinase Promotes the Migration of Melanoma Cells through Rho-mediated Actin Cytoskeleton Reorganization J. Biol. Chem., October 27, 2006; 281(43): 32574 - 32586. [Abstract] [Full Text] [PDF]

				H. Guo, H. Miao, L. Gerber, J. Singh, M. F. Denning, A. C. Gilliam, and B. Wang Disruption of EphA2 Receptor Tyrosine Kinase Leads to Increased Susceptibility to Carcinogenesis in Mouse Skin. Cancer Res., July 15, 2006; 66(14): 7050 - 7058. [Abstract] [Full Text] [PDF]

				D. B. Ramnarain, S. Park, D. Y. Lee, K. J. Hatanpaa, S. O. Scoggin, H. Otu, T. A. Libermann, J. M. Raisanen, R. Ashfaq, E. T. Wong, et al. Differential Gene Expression Analysis Reveals Generation of an Autocrine Loop by a Mutant Epidermal Growth Factor Receptor in Glioma Cells Cancer Res., January 15, 2006; 66(2): 867 - 874. [Abstract] [Full Text] [PDF]

				S. Abraham, D. W. Knapp, L. Cheng, P. W. Snyder, S. K. Mittal, D. S. Bangari, M. Kinch, L. Wu, J. Dhariwal, and S. I. Mohammed Expression of EphA2 and Ephrin A-1 in Carcinoma of the Urinary Bladder Clin. Cancer Res., January 15, 2006; 12(2): 353 - 360. [Abstract] [Full Text] [PDF]

				M. Parri, F. Buricchi, M. L. Taddei, E. Giannoni, G. Raugei, G. Ramponi, and P. Chiarugi EphrinA1 Repulsive Response Is Regulated by an EphA2 Tyrosine Phosphatase J. Biol. Chem., October 7, 2005; 280(40): 34008 - 34018. [Abstract] [Full Text] [PDF]

				J. Wykosky, D. M. Gibo, C. Stanton, and W. Debinski EphA2 as a Novel Molecular Marker and Target in Glioblastoma Multiforme Mol. Cancer Res., October 1, 2005; 3(10): 541 - 551. [Abstract] [Full Text] [PDF]

				C. N. Landen Jr., A. Chavez-Reyes, C. Bucana, R. Schmandt, M. T. Deavers, G. Lopez-Berestein, and A. K. Sood Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery Cancer Res., August 1, 2005; 65(15): 6910 - 6918. [Abstract] [Full Text] [PDF]

				H Iida, M Honda, H F Kawai, T Yamashita, Y Shirota, B-C Wang, H Miao, and S Kaneko Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma Gut, June 1, 2005; 54(6): 843 - 851. [Abstract] [Full Text] [PDF]

				H. Xu, W. Tian, J. N. Lindsley, T. T. Oyama, J. M. Capasso, C. J. Rivard, H. T. Cohen, S. M. Bagnasco, S. Anderson, and D. M. Cohen EphA2: expression in the renal medulla and regulation by hypertonicity and urea stress in vitro and in vivo Am J Physiol Renal Physiol, April 1, 2005; 288(4): F855 - F866. [Abstract] [Full Text] [PDF]

				V. J. Yao, M. G. Ozawa, M. Trepel, W. Arap, D. M. McDonald, and R. Pasqualini Targeting Pancreatic Islets with Phage Display Assisted by Laser Pressure Catapult Microdissection Am. J. Pathol., February 1, 2005; 166(2): 625 - 636. [Abstract] [Full Text] [PDF]

				T. Zhu, B. Starling-Emerald, X. Zhang, K.-O. Lee, P. D. Gluckman, H. C. Mertani, and P. E. Lobie Oncogenic Transformation of Human Mammary Epithelial Cells by Autocrine Human Growth Hormone Cancer Res., January 1, 2005; 65(1): 317 - 324. [Abstract] [Full Text] [PDF]

				C. J. Herrem, T. Tatsumi, K. S. Olson, K. Shirai, J. H. Finke, R. M. Bukowski, M. Zhou, A. L. Richmond, I. Derweesh, M. S. Kinch, et al. Expression of EphA2 is Prognostic of Disease-Free Interval and Overall Survival in Surgically Treated Patients with Renal Cell Carcinoma Clin. Cancer Res., January 1, 2005; 11(1): 226 - 231. [Abstract] [Full Text] [PDF]

				Z.-l. Yuan, Y.-j. Guan, L. Wang, W. Wei, A. B. Kane, and Y. E. Chin Central Role of the Threonine Residue within the p+1 Loop of Receptor Tyrosine Kinase in STAT3 Constitutive Phosphorylation in Metastatic Cancer Cells Mol. Cell. Biol., November 1, 2004; 24(21): 9390 - 9400. [Abstract] [Full Text] [PDF]

				M. Hu, K. L. Carles-Kinch, D. P. Zelinski, and M. S. Kinch EphA2 Induction of Fibronectin Creates a Permissive Microenvironment for Malignant Cells Mol. Cancer Res., October 1, 2004; 2(10): 533 - 540. [Abstract] [Full Text] [PDF]

				R. van Doorn, R. Dijkman, M. H. Vermeer, J. J. Out-Luiting, E. M. H. van der Raaij-Helmer, R. Willemze, and C. P. Tensen Aberrant Expression of the Tyrosine Kinase Receptor EphA4 and the Transcription Factor Twist in Sezary Syndrome Identified by Gene Expression Analysis Cancer Res., August 15, 2004; 64(16): 5578 - 5586. [Abstract] [Full Text] [PDF]

				P. H. Thaker, M. Deavers, J. Celestino, A. Thornton, M. S. Fletcher, C. N. Landen, M. S. Kinch, P. A. Kiener, and A. K. Sood EphA2 Expression Is Associated with Aggressive Features in Ovarian Carcinoma Clin. Cancer Res., August 1, 2004; 10(15): 5145 - 5150. [Abstract] [Full Text] [PDF]

				P. Dobrzanski, K. Hunter, S. Jones-Bolin, H. Chang, C. Robinson, S. Pritchard, H. Zhao, and B. Ruggeri Antiangiogenic and Antitumor Efficacy of EphA2 Receptor Antagonist Cancer Res., February 1, 2004; 64(3): 910 - 919. [Abstract] [Full Text] [PDF]

				P. M. S. Alves, O. Faure, S. Graff-Dubois, D.-A. Gross, S. Cornet, S. Chouaib, I. Miconnet, F. A. Lemonnier, and K. Kosmatopoulos EphA2 as Target of Anticancer Immunotherapy: Identification of HLA-A*0201-Restricted Epitopes Cancer Res., December 1, 2003; 63(23): 8476 - 8480. [Abstract] [Full Text] [PDF]

				R. L. Pratt and M. S. Kinch Ligand Binding Up-Regulates EphA2 Messenger RNA Through the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Pathway Mol. Cancer Res., December 1, 2003; 1(14): 1070 - 1076. [Abstract] [Full Text] [PDF]

				G. Zeng, Z. Hu, M. S. Kinch, C.-X. Pan, D. A. Flockhart, C. Kao, T. A. Gardner, S. Zhang, L. Li, L. A. Baldridge, et al. High-Level Expression of EphA2 Receptor Tyrosine Kinase in Prostatic Intraepithelial Neoplasia Am. J. Pathol., December 1, 2003; 163(6): 2271 - 2276. [Abstract] [Full Text]

				K. T. Coffman, M. Hu, K. Carles-Kinch, D. Tice, N. Donacki, K. Munyon, G. Kifle, R. Woods, S. Langermann, P. A. Kiener, et al. Differential EphA2 Epitope Display on Normal versus Malignant Cells Cancer Res., November 15, 2003; 63(22): 7907 - 7912. [Abstract] [Full Text] [PDF]

				Y.-R. Kao, J.-Y. Shih, W.-C. Wen, Y.-P. Ko, B.-M. Chen, Y.-L. Chan, Y.-W. Chu, P.-C. Yang, C.-W. Wu, and S. R. Roffler Tumor-associated Antigen L6 and the Invasion of Human Lung Cancer Cells Clin. Cancer Res., July 1, 2003; 9(7): 2807 - 2816. [Abstract] [Full Text] [PDF]

				M. Lu, K. D. Miller, Y. Gokmen-Polar, M.-H. Jeng, and M. S. Kinch EphA2 Overexpression Decreases Estrogen Dependence and Tamoxifen Sensitivity Cancer Res., June 15, 2003; 63(12): 3425 - 3429. [Abstract] [Full Text] [PDF]

				A. Palmer and R. Klein Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function Genes & Dev., June 15, 2003; 17(12): 1429 - 1450. [Full Text] [PDF]

				J. Walker-Daniels, A. R. Hess, M. J.C. Hendrix, and M. S. Kinch Differential Regulation of EphA2 in Normal and Malignant Cells Am. J. Pathol., April 1, 2003; 162(4): 1037 - 1042. [Full Text] [PDF]

				X. Zhang, T. Zhu, Y. Chen, H. C. Mertani, K.-O. Lee, and P. E. Lobie Human Growth Hormone-regulated HOXA1 Is a Human Mammary Epithelial Oncogene J. Biol. Chem., February 21, 2003; 278(9): 7580 - 7590. [Abstract] [Full Text] [PDF]

				M. S. Kinch, M.-B. Moore, and D. H. Harpole Jr. Predictive Value of the EphA2 Receptor Tyrosine Kinase in Lung Cancer Recurrence and Survival Clin. Cancer Res., February 1, 2003; 9(2): 613 - 618. [Abstract] [Full Text] [PDF]

				M. Koolpe, M. Dail, and E. B. Pasquale An Ephrin Mimetic Peptide That Selectively Targets the EphA2 Receptor J. Biol. Chem., November 27, 2002; 277(49): 46974 - 46979. [Abstract] [Full Text] [PDF]

				J. Walker-Daniels, D. J. Riese II, and M. S. Kinch c-Cbl-Dependent EphA2 Protein Degradation Is Induced by Ligand Binding Mol. Cancer Res., November 1, 2002; 1(1): 79 - 87. [Abstract] [Full Text] [PDF]

				K. D. Kikawa, D. R. Vidale, R. L. Van Etten, and M. S. Kinch Regulation of the EphA2 Kinase by the Low Molecular Weight Tyrosine Phosphatase Induces Transformation J. Biol. Chem., October 11, 2002; 277(42): 39274 - 39279. [Abstract] [Full Text] [PDF]

				K. Carles-Kinch, K. E. Kilpatrick, J. C. Stewart, and M. S. Kinch Antibody Targeting of the EphA2 Tyrosine Kinase Inhibits Malignant Cell Behavior Cancer Res., May 1, 2002; 62(10): 2840 - 2847. [Abstract] [Full Text] [PDF]

				N. D. Zantek, J. Walker-Daniels, J. Stewart, R. K. Hansen, D. Robinson, H. Miao, B. Wang, H.-J. Kung, M. J. Bissell, and M. S. Kinch MCF-10A-NeoST: A New Cell System for Studying Cell-ECM and Cell-Cell Interactions in Breast Cancer Clin. Cancer Res., November 1, 2001; 7(11): 3640 - 3648. [Abstract] [Full Text] [PDF]

				E. Malaga-Trillo and A. Meyer Genome Duplications and Accelerated Evolution of Hox Genes and Cluster Architecture in Teleost Fishes Integr. Comp. Biol., June 1, 2001; 41(3): 676 - 686. [Abstract] [Full Text] [PDF]