RASSF1A expression level in primary epithelial tumors of various locations

Abstract

Tumor suppressor activity of RASSF1A in vitro and in vivo was established, in particular, in studies of knockout mice cells. Data on methylation of the promoter region and a lower expression of RASSF1A were mostly obtained with cancer cell lines. Here, the RASSF1A mRNA was quantified the first time in primary epithelial malignant tumors of five various locations from 130 patients by semi-quantitative RT-PCR. Representative samples of kidney, lung, and breast carcinomas were examined. Preliminary data were obtained for RASSF1A expression in ovarian and colorectal carcinomas. System studies showed unexpected expression profiles, namely, the mRNA level increased (two- to sevenfold) more frequently than decreased in renal, breast, ovarian, and colorectal carcinomas. A higher RASSF1A mRNA level was significantly more frequent in renal cell carcinomas (24/38, 63% vs 8/38, 21%, P = 0.0004 by Fisher’s exact test) and ovarian carcinomas (8/13, 62% vs 2/13, 15%, P = 0.0114). Equal frequencies of lower and higher RASSF1A expression levels were only observed in non-small cell lung cancer (16/38, 42%). Noteworthy, an increase in expression was more common at early clinical stages of squamous cell lung cancer and adenocarcinoma, while a decrease in RASSF1A expression was more frequent at advanced clinical stages. In clear cell renal cell carcinoma, an increase in RASSF1A expression occurred more often at both early and advanced stages and was significant at advanced stages (P = 0.0094). The findings suggested tumor specificity for changes in RASSF1A expression. The observed regularities may also indicate that RASSF1A has dual functions in tumors, acting as a tumor suppressor and as a protooncogene.