title: MDM2 expression and regulation in prostate cancer racial disparity.
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.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, NYU Cancer Institute, New York University School of Medicine, New York, New York, USA.
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.forename: Elnaz F
authors.initials: EF
authors.lastname: Firoz
authors.forename: Amy
authors.initials: A
authors.lastname: Rose
authors.forename: Elen
authors.initials: E
authors.lastname: Blochin
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Danuta
authors.initials: D
authors.lastname: Pollens
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.forename: Carole
authors.initials: C
authors.lastname: Oddoux
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.forename: Iman
authors.initials: I
authors.lastname: Osman