Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

• Published in: Molecular carcinogenesis 1997-07, Vol.19 (3), p.165-175
• Main Authors: Marengo, Susan Ruth, Sikes, Robert A., Anezinis, Ploutarchos, Chang, Shi-ming, Chung, Leland W. K.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma - secondary; Animals; Cell Transformation, Neoplastic; Epithelium - metabolism; Epithelium - pathology; erB-2; Male; metastasis; Mice; Mice, Nude; Muscle Neoplasms - secondary; Muscle, Skeletal - pathology; Mutation; Neoplasm Transplantation; p185neu-T; Phenotype; prostate; Prostate - metabolism; Prostate - pathology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Rats; Rats, Inbred Strains; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - genetics; Transfection; Tumor Cells, Cultured
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/(SICI)1098-2744(199707)19:3<165::AID-MC4>3.0.CO;2-D

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 × 106 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 (12 500 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 ≤ 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. Mol. Carcinog. 19:165–175, 1997. © 1997 Wiley‐Liss, Inc.