Functional characterization of THY1 (CD90) gene mediated by shRNA in pancreatic cancer cell lines

Abstract

Pancreatic cancer is one of the most life-threatening neoplasias and its prognosis has not been improved despite advances in diagnostic and therapeutic strategies. Because the disease is usually diagnosed at advanced tumor stages, patients have a median survival of <1 year; only 5% of patients are alive 5 years after diagnosis. The main reasons for these findings are resistance against conventional therapy and tumor re-growth attributed to the existence of cancer stem cells (CSC), which occupy only a small part of the entire cancer tissue. CSC has characteristic features such as chemoresistance, ability to metastasize and to reconstruct a hierarchical population of tumor cells. Thymocyte differentiation antigen 1 (THY1), also known as CD90, is a regulator of cell-cell and cell-matrix interactions that plays an important role in metastasis and inflammation; increased expression of CD90 was shown to be associated with disease progression, invasive potential, metastasis and drug resistance. Recently, CD90 has also received attention as a CSC marker in various tumors, including in pancreatic adenocarcinomas. RNA interference (RNAi) is a ubiquitous mechanism of eukaryotic gene regulation and an excellent strategy for specific gene silencing. The present study aims to elucidate the effect of stable shRNA-mediated gene THY1 (CD90) silencing in adenocarcinomas pancreatic cell lines and evaluate some molecular mechanisms associated with this neoplasia, such as apotosis, invasive properties, potential of celular transformation and proliferative capacity. (AU)