Detailed analysis of expression and promoter methylation status of apoptosis-related genes in prostate cancer

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Carvalho, JR (Author) Other; Filipe, L (Author) Other; Costa, VL (Author) Other; Ribeiro, FR (Author) Other; Martins, AT (Author) Other; Manuel R Teixeira (Author) ICBAS; Carmen Jeronimo (Author) ICBAS; henrique, rmf (Author) ICBAS

Journal

Title: APOPTOSIS

Vol. 15

Pages: 956-965

ISSN: 13608185

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 28 Citations

Scopus - 34 Citations

Other information

Authenticus ID: P-003-43S

DOI: 10.1007/s10495-010-0508-6

Abstract (EN): Apoptosis is known to be involved in tumorigenesis and a defective ratio between cell proliferation and apoptosis may contribute to the emergence of a malignant phenotype. Transcriptional silencing of apoptosis-related genes associated with aberrant promoter methylation may impair the apoptotic machinery, ultimately leading to cancer development. Aberrant promoter methylation of numerous genes involved in many different pathways is frequent in prostate cancer. Our aim was to quantitatively assess the methylation status of several apoptosis-related genes in prostate adenocarcinoma (PCa) and its precursor lesion, high-grade prostatic intraepithelial neoplasia (HGPIN). First, 120 PCa and 39 HGPIN were screened for altered expression of BCL2, CASP8, CASP3, DAPK DR3, DR4, DR6, FAS, TMS1, TNFR2, using 28 benign prostate hyperplasias and 10 normal prostates as controls. Underexpressed genes were then assessed by quantitative methylation-specific PCR to determine the promoter methylation status. Finally, quantitative mRNA expression of aberrantly methylated genes was performed and methylation data was correlated with standard clinicopathologic parameters. DAPK, DR4 and TNFR2 were significantly overexpressed in HGPIN and PCa, whereas BCL2, TMS1, and FAS were downregulated. Although methylation levels were significantly higher for TMS1 and BCL2 (correlating with advanced stage), an inverse correlation with mRNA expression was found only for BCL2. We concluded that the apoptotic pathways are largely preserved in prostate carcinogenesis, in particular the extrinsic pathway, with the exception of FAS and TMS1, which are epigenetically downregulated. In addition, BCL2 was also found to be frequently silenced in PCa due to aberrant promoter methylation, thus supporting a future role for apoptosis-targeted therapy in prostate cancer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10