METASTASIS INDUCED BY OVEREXPRESSION OF P185(NEU-T) AFTER ORTHOTOPIC INJECTION INTO A PROSTATIC EPITHELIAL-CELL LINE (NBE)

Overexpression of p185(erbB2/neu) has been detected in many adenocarci nomas, including prostatic cancer. In this study, a nontumorigenic cel l line isolated from the rat prostatic epithelium (NbE) transfected wi th the activated oncogene p185(neu-T) was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p18 5(neu-T) were injected orthotopically (1.5 to 2 x 10(6) cells) into th e dorsal-lateral prostates of nude mice, prostatic tumors were detecte d in all mice injected and metastasis to the skeletal muscle in the ri b area in 60-80% of the mice injected. Tumor and metastasis origin was confirmed by reselection with G418 and reverse transcriptase-polymera se chain reaction. Control cell lines produced no prostatic tumors or metastases. Incubation at low density (12 500 cells/2 cm(2)) in serum- free medium revealed that clones overexpressing p185(neu-T) had a high er rate of [H-3]thymidine incorporation than did control clones on 3, 5, and 7 d after plating (P less than or equal to 0.0001) and constitu tively overexpressed the 2.6-kb ornithine decarboxylase transcript. Ad ditionally, clones overexpressing p185(neu-T) demonstrated an increase d expression of epidermal growth factor receptor and p180(erbB4), as j udged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185(neu-T) fosters tumor progression by sever al pathways, including induction of the metastatic cascade, increased proliferative capabilities, and increased expression of other members of the erbB2 gene family. (C) 1997 Wiley-Liss, Inc.