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Home | The Scope | What's New | Grand Rounds | Research In Progress RESEARCH IN PROGRESS PRESENTATION "Biliary Cell Transformation" November 14, 2005 Toru Asano, MD, PhD, Post-Doctoral Fellow, Division of Cellular and Molecular Pathogenesis, presented his research in progress on the topic of "Biliary Cell Transformation". His abstract on this topic follows: Cholangiocarcinoma (ChC) is a highly malignant cancer arising within the intra- and extra-hepatic biliary tract, and is considered to originate from transformed bile duct epithelial cells (cholangiocytes). In the last 20 years, both the incidence and mortality rates of ChC have been increasing worldwide. In most cases, however, the basis for this increase is unknown. ChCs often develop under the backdrop of chronic inflammatory disease of the biliary tree, with impairment of bile flow. Epidermal growth factor (EGF) has been demonstrated to be significantly increased in the livers of bile duct obstructed rats, and bile acids, which are also altered during biliary obstruction, have been shown to transactivate the EGF receptor (EGFR) in cholangiocytes. Both EGF and bile acids can also stimulate cholangiocyte and cholangiocarcinoma cell proliferation in vitro. In the present study, an untransformed rat cholangiocyte cell line, designated as BDE1, was cultured in DMEM medium containing 10% FBS with or without 25 ng/ml EGF, and allowed to remain in confluence for two weeks before subsequent cell passages (selective culture conditions) to determine if: 1) cholangiocytes can undergo spontaneous malignant transformation in vitro, 2) EGF can enhance spontaneous malignant transformation of these cells. P assage 11 BDE1 cells cultured under selective culture conditions in the presence of EGF ( BDE/E p11 cells) showed strong colony forming efficiency in soft agar, suggesting the possibility that BDE/E p11 cells may have the potential for tumorigenicity. BDE/E p11 (SA) cells, a monolayer cell line derived from soft agar colonies of BDE/E p11 cells, showed overexpression of EGFR protein by Western blotting. BDE/E p11 (SA) cells also showed higher expression of phosphorylated EGFR and COX-2 protein compared with the control cell line; p assage 1 BDE1 cells cultured under selective culture conditions in the absence of EGF (BDE p1 cells) . Moreover, while cell growth of BDE p1 cells was inhibited by TGF- β 1 treatment, BDE/E p11 (SA) cells acquired resistance to TGF- β 1-induced cell growth inhibition. These results also suggest that BDE/E p11 (SA) cells may be spontaneously transformed. Tumorigenicity experiments of these cell lines are currently ongoing to validate this possibility. Preliminary results from the tumorigenicity experiments have demonstrated BDE/E p11 (SA) cells to be tumorigenic when transplanted into the liver of an isogenic rat. From the laboratory of Dr. Alphonse E. Sirica For a printable version of this Research in Progress presentation, click here. For more information visit the Division of Cellular and Molecular Pathogenesis web page. For more information about VCU Pathology
Research in Progress presentations contact Updated November 23, 2005 |
