METASTATIC SUBLINES OF AN SV40 LARGE T-ANTIGEN IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELL LINE

BACKGROUND. The available human prostate cancer cell lines that are me tastatic in athymic nude mice all have complex, highly aneuploid karyo types. Other prostatic cells immortalized by transforming genes of SV4 0 or HPV and converted to tumorigenicity by additional genetic manipul ation are not reported to be metastatic. METHODS. Tumorigenic sublines of human prostate epithelial cells previously immortalized by transfe ction with the SV40T antigen gene were obtained by sequential passage in male athymic nude mice. These sublines were evaluated histopatholog ically for tumorigenicity and metastasis in athymic nude mice after su bcutaneous, intraperitoneal, and intraprostatic injection. Each sublin e was characterized by standard (GTG-banding) cytogenetic and FISH ana lysis, and RNase protection assays for androgen receptor expression. R ESULTS. Two sublines produced metastases in lungs and the diaphragm of most mice after either intraprostatic or intraperitoneal injection. T he M2205 subline formed large local tumors after intraprostatic inject ion. Cytogenetic aberrations present in the metastatic sublines, but n ot in the tumorigenic, nonmetastatic lines or the parental P69SV40T li ne, included dup(11)(q14q22), der(16) t (16;19) (q24;q13.1), which res ulted in the loss of the short arm and proximal long arm of chromosome 19 (19q13.1-->19pter), and loss of the Y chromosome. None of the subl ines expressed the androgen receptor. CONCLUSIONS. These cytogenetical ly defined, SV40T-immortalized human prostate epithelial cell lines, w ith distinct biological behaviors in vivo, provide additional tools fo r the genetic analysis of the emergence of metastatic capacity. (C) 19 98 Wiley-Liss, Inc.