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

Jason D. Engel, Shilajit D. Kundu, Tony Yang, Sharon Lang, Shannon Goodwin, Lynn Janulis, Jin Seon Cho, Jay Chang, Seong Jin Kim, Chung Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalUrology
Volume54
Issue number1
DOIs
StatePublished - Jul 1 1999

ASJC Scopus subject areas

  • Urology

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