Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)
✍ Scribed by Susan Ruth Marengo; Robert A. Sikes; Ploutarchos Anezinis; Shi-ming Chang; Leland W. K. Chung
- Book ID
- 101270424
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 430 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
Overexpression of p185 erbB2/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 p185 neu-T was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p185 neu-T were injected orthotopically (1.5 to 2 × 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 (12 500 cells/2 cm 2 ) in serum-free medium revealed that clones overexpressing p185 neu-T had a higher rate of [ 3 H]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 p185 neu-T demonstrated an increased expression of epidermal growth factor receptor and p180 erbB4 , as judged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185 neu-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.