Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE).
Overexpression of p185erbB2/neu has been detected in many adenocarcinomas, including prostatic cancer. In this study, a nontumorigenic cell line isolated from the rat prostatic epithelium (NbE) transfected with the activated oncogene p185neu-T was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p185neu-T were injected orthotopically (1.5 to 2 x 10(6) cells) into the dorsal-lateral prostates of nude mice, prostatic tumors were detected in all mice injected and metastasis to the skeletal muscle in the rib area in 60-80% of the mice injected. Tumor and metastasis origin was confirmed by reselection with G418 and reverse transcriptase-polymerase chain reaction. Control cell lines produced no prostatic tumors or metastases. Incubation at low density (12500 cells/2 cm2) in serum-free medium revealed that clones overexpressing p185neu-T had a higher rate of [3H]thymidine incorporation than did control clones on 3, 5, and 7 d after plating (P < or = 0.0001) and constitutively overexpressed the 2.6-kb ornithine decarboxylase transcript. Additionally, clones overexpressing p185neu-T demonstrated an increased expression of epidermal growth factor receptor and p180erbB4, as judged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185neu-T fosters tumor progression by several pathways, including induction of the metastatic cascade, increased proliferative capabilities, and increased expression of other members of the erbB2 gene family.
Marengo
S R
SR
Jim and Eilleen Dicke Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4931, USA.
Sikes
R A
RA
Anezinis
P
P
Chang
S M
SM
Chung
L W
LW
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019042:Muscle Neoplasms / Q000556:secondary*; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009368:Neoplasm Transplantation; D010641:Phenotype; D011467:Prostate / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D018719:Erb-b2 Receptor Tyrosine Kinases