Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (Renca) cells.
OBJECTIVE
To demonstrate that the introduction of the transforming growth factor-beta (TGF-beta) type II receptor (TbetaR-II) decreases tumorigenicity in an aggressive murine renal carcinoma line, Renca. These cells do not express TbetaR-II. Because the presence of TbetaR-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 TbetaR-II as a tumor suppressor gene.


METHODS
Renca cells were stably transfected with a retrovirus-mediated TbetaR-II expression vector. In vitro sensitivity to growth inhibitory effect of TGF-beta 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 TbetaR-II transfected cells was tested. Wild-type Renca cells and cells transfected with the control vector were also tested for comparison.


RESULTS
Expression of TbetaR-II mRNA was evident in Renca cells after transfection with the TbetaR-II construct. In vitro sensitivity to the growth inhibitory effect of TGF-beta was restored. This effect of TGF-beta was reversible with a neutralizing antibody specific for the extracellular domain of TbetaR-II. Xenografts grown from TbetaR-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 TbetaR-II is a central mediator of tumorigenicity in Renca cells. As with other tumor suppressor genes, the loss of TbetaR-II expression allows for the development of an aggressive phenotype.
Engel
J D
JD
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Kundu
S D
SD
Yang
T
T
Lang
S
S
Goodwin
S
S
Janulis
L
L
Cho
J S
JS
Chang
J
J
Kim
S J
SJ
Lee
C
C
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002455:Cell Division; D051379:Mice; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II