This Article Full Text Full Text (PDF) Supplementary Data 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 Yang, B. Articles by Longley, B. J. Search for Related Content PubMed PubMed Citation Articles by Yang, B. Articles by Longley, B. J.

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines

¹ Department of Dermatology and ² Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin Medical School, Madison, Wisconsin; ³ The Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering Cancer Institute, New York, New York; ⁴ California Pacific Medical Center Research Institute, San Francisco, California; and ⁵ The Wistar Institute, Philadelphia, Pennsylvania

Requests for reprints: Bing Yang and B. Jack Longley, Department of Dermatology, University of Wisconsin Medical School, Room B25, 1300 University Avenue, Madison, WI 53706. Phone: 608-263-7144; Fax: 608-263-5223; E-mail: byang{at}dermatology.wisc.edu.

The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A–positive, p53^wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A–positive HCT 116 p53^–/– variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies. [Cancer Res 2007;67(20):9954–62]

This article has been cited by other articles:

				P.-C. Chang, L. D. Fitzgerald, A. Van Geelen, Y. Izumiya, T. J. Ellison, D.-H. Wang, D. K. Ann, P. A. Luciw, and H.-J. Kung Kruppel-Associated Box Domain-Associated Protein-1 as a Latency Regulator for Kaposi's Sarcoma-Associated Herpesvirus and Its Modulation by the Viral Protein Kinase Cancer Res., July 15, 2009; 69(14): 5681 - 5689. [Abstract] [Full Text] [PDF]

				S. Cheng, W. Liu, M. Mercado, S. Ezzat, and S. L Asa Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer Endocr. Relat. Cancer, June 1, 2009; 16(2): 455 - 466. [Abstract] [Full Text] [PDF]

				W. Liu, S. Cheng, S. L. Asa, and S. Ezzat The Melanoma-Associated Antigen A3 Mediates Fibronectin-Controlled Cancer Progression and Metastasis Cancer Res., October 1, 2008; 68(19): 8104 - 8112. [Abstract] [Full Text] [PDF]

				M. F. Gjerstorff, L. Harkness, M. Kassem, U. Frandsen, O. Nielsen, M. Lutterodt, K. Mollgard, and H. J. Ditzel Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation Hum. Reprod., October 1, 2008; 23(10): 2194 - 2201. [Abstract] [Full Text] [PDF]