Original Article MDM2 expression and regulation in prostate cancer racial disparity
Guimin Wang, Elnaz F. Firoz, Amy Rosea, Elen Blochin, Paul Christos, Danut Pollens, Madhu Mazumdar, William Gerald, Carole Oddoux, Peng Lee, Iman Osman
The Ronald O. Perelman Department of Dermatology, Department of Pathology, Human Genetics Program of Pediatrics, Department of Medicine and Urology, NYU Cancer Institute, New York University School of Medicine, New York, New York. Department of Public Health and Divisions of Biostatistics, New York-Presbyterian Hospital and Weill-Cornell Medical College, New York, New York. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. New York, New York.
Received 4 November 2008; Accepted 14 November 2008; Available online 4 December 2008
Abstract: MDM2 is a key negative regulator of tumor suppressor p53. A single nucleotide polymorphism in the MDM2 promoter, SNP309, enhances transcriptional activation of MDM2 and has been associated with early onset of several types of cancer. In this study, we attempted to determine if the MDM2 SNP309 polymorphism plays a role in the aggressive phenotype seen in African American (AA) prostate cancer by examining the association between MDM2 SNP309 and MDM2 protein levels in prostate cancer (PCa) patients of different racial backgrounds. Prospectively enrolled PCa patients (AA=51, CA=50) were evaluated for MDM2 SNP309 and MDM2 protein expression. MDM2 overexpression, defined as >10% of tumor cells in three tissue cores, was assessed using immunohistochemistry on tissue microarray. MDM2 protein expression was significantly greater in CA than AA patients (78% versus 45% respectively, p=0.0007). Germline DNA was analyzed by PCR-RFLP then confirmed by DNA sequencing. MDM2 SNP309 genotype frequencies did not differ significantly between AA and CA PCa patients (AA: TT 68.6%, TG 25.5%, GG 5.9%; CA: TT 62.0%, TG 20.0%, GG 18.0%; p=0.16), suggesting that the MDM2 SNP309 allele does not play a significant role in the observed overexpression. (IJCEP811002).
Key Words: MDM2, prostate cancer, single nucleotide polymorphism, SNP309
Address all correspondence to: Peng Lee, MD, PhD, Department of Pathology, New York University School of Medicine, New York Harbor Healthcare System, 423 E. 23rd street, Room6140N, New York, NY 10010, Phone: (212) 951-3418, Fax: (212) 951-6341, E-mail: Peng.Lee@med.nyu.edu