Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (renca) cells

• Published in: Urology (Ridgewood, N.J.) Vol. 54; no. 1; pp. 164 - 170
• Main Authors: Engel, Jason D, Kundu, Shilajit D, Yang, Tony, Lang, Sharon, Goodwin, Shannon, Janulis, Lynn, Cho, Jin Seon, Chang, Jay, Kim, Seong-Jin, Lee, Chung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1999
• Subjects: Animals; Carcinoma, Renal Cell - pathology; Cell Division; Mice; Mice, Nude; Protein-Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta - biosynthesis; Receptors, Transforming Growth Factor beta - physiology; RNA, Messenger - analysis; Transfection; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - physiology; Tumor Cells, Cultured
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(99)00093-X

Objectives. To demonstrate that the introduction of the transforming growth factor-beta (TGF-β) type II receptor (TβR-II) decreases tumorigenicity in an aggressive murine renal carcinoma line, Renca. These cells do not express TβR-II. Because the presence of TβR-II in benign epithelial cells is ubiquitous, the ability to restore tumor suppressor activity in the Renca cell line with its introduction would elucidate the role of TβR-II as a tumor suppressor gene. Methods. Renca cells were stably transfected with a retrovirus-mediated TβR-II expression vector. In vitro sensitivity to growth inhibitory effect of TGF-β was assessed by the 3H-thymidine incorporation assay. For in vivo testing, xenograft tumors were produced by subcutaneous injection of tumor cells into immunodeficient nude mice. The tumorigenicity of these TβR-II transfected cells was tested. Wild-type Renca cells and cells transfected with the control vector were also tested for comparison. Results. Expression of TβR-II mRNA was evident in Renca cells after transfection with the TβR-II construct. In vitro sensitivity to the growth inhibitory effect of TGF-β was restored. This effect of TGF-β was reversible with a neutralizing antibody specific for the extracellular domain of TβR-II. Xenografts grown from TβR-II transfected cells were significantly smaller, weighed less, and developed tumors later than those developed from wild-type Renca cells and those transfected with the control vector. Conclusions. We conclude that TβR-II is a central mediator of tumorigenicity in Renca cells. As with other tumor suppressor genes, the loss of TβR-II expression allows for the development of an aggressive phenotype.