Expression of cytokeratin-19 as a marker of neoplastic progression of human prostate epithelial cells.

Abstract

Our earlier studies demonstrated neoplastic transformation of SV40-immortalized neonatal human prostate epithelial cells (267B1) by fractionated doses of ionizing radiation or by introduction of v-ki-ras oncogene. X-ray-treated 267B1 cells represent three different stages of neoplastic progression: nontumorigenic F3-SAC cells that acquired morphological changes and anchorage independence when treated with 2 x 2 Gy of X-rays; malignantly transformed 267B1-XR and 267B1-SXR cells that received 2-Gy doses to a total of 30 Gy. We also reported alterations in cell size, morphology, actin stress fibers, and levels of actin-binding proteins in these transformed human prostate cells. We analyzed intermediate filament-nuclear matrix (IF-NM) protein expression in the various 267B1 cells as a consequence of neoplastic progression by two-dimensional gel electrophoresis and immunofluorescence. Our present study revealed that the 267B1 cells experienced progressive changes in their intermediate filament protein composition during the process of neoplastic conversion, achieved either by X-rays or by ras-oncogene. In particular, we observed a stepwise downregulation of cytokeratin-19 in these in vitro transformed 267B1 cells. Our data suggest that loss of expression of cytokeratin-19 accompanied the morphological alterations associated with in vitro neoplastic transformation of SV40-immortalized prostate epithelial cells.