This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ellerhorst, J. A. Articles by Grimm, E. A. Search for Related Content PubMed PubMed Citation Articles by Ellerhorst, J. A. Articles by Grimm, E. A. Social Bookmarking                            What's this?

Loss of MDA-7 Expression With Progression of Melanoma

From the Departments of Molecular and Cellular Oncology, Pathology, and Biostatistics, The University of Texas M.D. Anderson Cancer Center, and Introgen Therapeutics, Houston, TX.

Address reprint requests to Julie A. Ellerhorst, MD, PhD, Department of Molecular and Cellular Oncology, Box 79, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4095; email: jaellerh{at}mail.mdanderson.org

PURPOSE: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival.

MATERIALS AND METHODS: MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling.

RESULTS: Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases.

CONCLUSION: Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma.

Both V.G.P. and S.E. contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. A. Park, T. Walker, A. P. Martin, J. Allegood, N. Vozhilla, L. Emdad, D. Sarkar, M. Rahmani, M. Graf, A. Yacoub, et al. MDA-7/IL-24-induced cell killing in malignant renal carcinoma cells occurs by a ceramide/CD95/PERK-dependent mechanism Mol. Cancer Ther., May 1, 2009; 8(5): 1280 - 1291. [Abstract] [Full Text] [PDF]

				M. Zheng, D. Bocangel, R. Ramesh, S. Ekmekcioglu, N. Poindexter, E. A. Grimm, and S. Chada Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells Mol. Cancer Ther., December 1, 2008; 7(12): 3842 - 3851. [Abstract] [Full Text] [PDF]

				A. Sainz-Perez, H. Gary-Gouy, F. Gaudin, G. Maarof, A. Marfaing-Koka, T. de Revel, and A. Dalloul IL-24 Induces Apoptosis of Chronic Lymphocytic Leukemia B Cells Engaged into the Cell Cycle through Dephosphorylation of STAT3 and Stabilization of p53 Expression J. Immunol., November 1, 2008; 181(9): 6051 - 6060. [Abstract] [Full Text] [PDF]

				A. Yacoub, M. A. Park, P. Gupta, M. Rahmani, G. Zhang, H. Hamed, D. Hanna, D. Sarkar, I. V. Lebedeva, L. Emdad, et al. Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells Mol. Cancer Ther., February 1, 2008; 7(2): 297 - 313. [Abstract] [Full Text] [PDF]

				A. Yacoub, P. Gupta, M. A. Park, M. Rhamani, H. Hamed, D. Hanna, G. Zhang, D. Sarkar, I. V. Lebedeva, L. Emdad, et al. Regulation of GST-MDA-7 toxicity in human glioblastoma cells by ERBB1, ERK1/2, PI3K, and JNK1-3 pathway signaling Mol. Cancer Ther., February 1, 2008; 7(2): 314 - 329. [Abstract] [Full Text] [PDF]

				P. B. Fisher Is mda-7/IL-24 a "Magic Bullet" for Cancer? Cancer Res., November 15, 2005; 65(22): 10128 - 10138. [Abstract] [Full Text] [PDF]

				S. Ishikawa, T. Nakagawa, R. Miyahara, Y. Kawano, K. Takenaka, K. Yanagihara, Y. Otake, H. Katakura, H. Wada, and F. Tanaka Expression of MDA-7/IL-24 and Its Clinical Significance in Resected Non-Small Cell Lung Cancer Clin. Cancer Res., February 1, 2005; 11(3): 1198 - 1202. [Abstract] [Full Text] [PDF]

				S. Aggarwal, Y. Takada, A. M. Mhashilkar, K. Sieger, S. Chada, and B. B. Aggarwal Melanoma Differentiation-Associated Gene-7/IL-24 Gene Enhances NF-{kappa}B Activation and Suppresses Apoptosis Induced by TNF J. Immunol., October 1, 2004; 173(7): 4368 - 4376. [Abstract] [Full Text] [PDF]

				A. J. Miller, J. Du, S. Rowan, C. L. Hershey, H. R. Widlund, and D. E. Fisher Transcriptional Regulation of the Melanoma Prognostic Marker Melastatin (TRPM1) by MITF in Melanocytes and Melanoma Cancer Res., January 15, 2004; 64(2): 509 - 516. [Abstract] [Full Text] [PDF]

				I. V. Lebedeva, Z.-Z. Su, D. Sarkar, S. Kitada, P. Dent, S. Waxman, J. C. Reed, and P. B. Fisher Melanoma Differentiation Associated Gene-7, mda-7/Interleukin-24, Induces Apoptosis in Prostate Cancer Cells by Promoting Mitochondrial Dysfunction and Inducing Reactive Oxygen Species Cancer Res., December 1, 2003; 63(23): 8138 - 8144. [Abstract] [Full Text] [PDF]

				R. Ramesh, A. M. Mhashilkar, F. Tanaka, Y. Saito, C. D. Branch, K. Sieger, J. B. Mumm, A. L. Stewart, A. Boquio, L. Dumoutier, et al. Melanoma Differentiation-associated Gene 7/Interleukin (IL)-24 Is a Novel Ligand That Regulates Angiogenesis via the IL-22 Receptor Cancer Res., August 15, 2003; 63(16): 5105 - 5113. [Abstract] [Full Text] [PDF]

				A. Yacoub, C. Mitchell, A. Lister, I. V. Lebedeva, D. Sarkar, Z.-Z. Su, C. Sigmon, R. McKinstry, V. Ramakrishnan, L. Qiao, et al. Melanoma Differentiation-associated 7 (Interleukin 24) Inhibits Growth and Enhances Radiosensitivity of Glioma Cells in Vitro and in Vivo Clin. Cancer Res., August 1, 2003; 9(9): 3272 - 3281. [Abstract] [Full Text] [PDF]

				S. Ekmekcioglu, J. A. Ellerhorst, J. B. Mumm, M. Zheng, L. Broemeling, V. G. Prieto, A. L. Stewart, A. M. Mhashilkar, S. Chada, and E. A. Grimm Negative Association of Melanoma Differentiation-associated Gene (mda-7) and Inducible Nitric Oxide Synthase (iNOS) in Human Melanoma: MDA-7 Regulates iNOS Expression in Melanoma Cells Mol. Cancer Ther., January 1, 2003; 2(1): 9 - 17. [Abstract] [Full Text] [PDF]