Significant Inhibition of Tumor-Suppressor Genes in Renal Cell Carcinoma
SR Scrape, H Zhang, C Xie, N Gokden, C-Y Fan. University of Arkansas for Medical Sciences, Little Rock, AR; John L. McClellan Memorial Veterans Hospital, Little Rock, AR
Background: One of the mechanisms involved in carcinogenesis is somatic mutation and subsequent inhibition of tumor suppressor genes enabling tumor cell growth in an uncontrolled manner. CDH1 or E-cadherin is an important gene that helps neighboring cells stick to one another (cell adhesion). It is believed that CDH1 acts as a tumor suppressor gene. Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine kinase and possesses apoptotic and tumor-suppressive functions. The Ras association domain family 1A gene (RASSF1A) is a recently discovered tumor suppressor whose inactivation is implicated in the development of many human cancers. In this study, we analyze gene expression levels of 3 important tumor suppressor genes, CDH1, DAPK and RASSF1A in clear cell renal cell carcinoma (CC-RCC) as compared to matched normal renal parenchyma.
Design: Total RNA was extracted from 14 fresh CC-RCC samples and their matched benign renal parenchyma. Gene expression levels for CDH1, DAPK and RASSF1A genes were analyzed by real-time RT-PCR Quantitation with the ABI Fast 7500 Real-time PCR System using Taqman -actin as an internal control for normalization.
Results: The mRNA expression levels are significantly lower in CC-RCC than those seen in adjacent normal parenchyma in 12 of 14 cases (85.7%) for the CDH1 gene, 11 of 14 cases (78.5%) for the DAPK gene and 12 of 14 cases (85.7%) for the RASSF1A gene. Overall, the mRNA expression levels in CC-RCC is about 32% for the CDH1 gene, 16% for the DAPK gene and 35% for the RASSF1A gene of those seen in normal renal tissues. Mean relative mRNA levels for CDH1, DAPK and RASSF1A in all 14 cases are1.0, 2.0 and 3.9 respectively as compared to a mean of 3.2, 12.9 and 11.0 for normal renal parenchyma. The differences in mRNA expression between CC-RCC and adjacent normal tissues for CDH1, DAPK and RASSF1A genes are statistically very significant (p <0.01).
Conclusions: Significant inhibition of tumor suppressor genes occurs commonly in CC-RCC as seen in 85.7% cases for the CDH1 gene, 78.5% cases for the DAPK gene and 85.7% cases for the RASSF1A gene. These results support that the three tumor suppressor genes, CDH1, DAPK and RASSF1A, play significant roles in the development and/or progression of renal cell carcinoma.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 136, Monday Morning