engleski

Expression of NF2 isoforms in sporadic colon cancer

NF2 gene was first described in association with an inherited cancer predisposition syndrome neurofibromatosis 2 (NF2), which predisposes individuals to the development of specific types of tumors of the nervous system, including schwannomas, meningiomas and ependymomas. NF2 protein product merlin is predominantly localized to the membrane-cytoskeleton interface where it participates in cell growth regulation. Although the mechanisms by which merlin acts to regulate cell growth are not entirely clear, a number of studies have suggested that merlin activity might depend on processes that link growth factor and ECM signaling to the actin cytoskeleton. Indeed, it has been shown recently that merlin inhibits Ras and Rac activation by uncoupling them from growth factor signals. Since these processes are essential for tumorigenesis and metastasis in general, we decided to examine the possible role of NF2 in sporadic colon cancer through analysis of its mRNA expression. The NF2 gene ( 22q12) is composed of 17 exons, with two alternatively spliced major isoforms, type I and II. Isoform type I lacks exon 16, whereas isoform type II contains exon 16 but lacks exon 17. These isoforms are variably expressed in some tissue types with possibly different functions. Real-time PCR was used to determine the NF2 mRNA expression, as well as expression of its mRNA isoforms type I and II in 60 pairs of colon cancer tumors and corresponding normal tissue. No statistically significant difference in total expression of NF2 gene as well as its isoforms I and II was observed in tumor tissue as compared to corresponding normal tissue. Results of mRNA expression were correlated with the patients' clinicopathological features. Expression of NF2 mRNA, as well as its isoforms I and II, was higher in moderately and poorly differentiated tumors and tumors classified as Dukes' C. Based on our results we can conclude that NF2 gene is involved in sporadic colon cancer development and progression.

NF2; mRNA isoforms; sporadic colorectal cancer

nije evidentirano