gas6 and the receptor tyrosine kinase axl in clear cell renal cell carcinomagas6受体酪氨酸激酶妳在透明细胞肾细胞癌.pdfVIP

Gas6 and the Receptor Tyrosine Kinase Axl in Clear Cell Renal Cell Carcinoma 1. ¨ 2. ¨ 3 ˚ 2 ¨ ¨ 1 Anna Gustafsson , Anna-Karin Bostrom , Borje Ljungberg , Hakan Axelson , Bjorn Dahlback * ¨ ¨ 1 Department of Laboratory Medicine, Section for Clinical Chemistry, University Hospital Malmo, Lund University, Malmo, Sweden, 2 Department of Laboratory Medicine, ¨ ¨ Center for Molecular Pathology, University Hospital Malmo, Lund University, Malmo, Sweden, 3 Department of Surgical and Perioperative Sciences, Urology and ˚ ˚ Andrology, Umea University, Umea, Sweden Abstract Background: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. Principal Findings: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells