Abstract
Findings of increased numbers of epidermal growth factor receptors (EGF-R) and increased expression of transforming growth factor α (TGF-α) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF-α in an autocrine manner. In the studies presented here, we have examined this hypothesis using two human renal carcinoma cell lines, SKRC-4 and SKRC-29. We demonstrated that both SKRC-4 and SKRC-29 cells were growth stimulated by >35% when cultured in the presence of TGF-α or EGF and were inhibited by 29% to 46% if cultured in the presence of anti-EGF-R monoclonal antibody 225. Treatment of cells with TGF-α enhanced the levels of expression of EGF-R mRNA and TGF-α mRNA. In addition, incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF-α species in the culture medium. Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF-α and that this regulatory pathway can be interrupted using antibody to its receptor, EGF-R.
Footnotes
-
↵1 This work was supported by Grants CA-42060 and CA-37641 from the NIH. I. A. is a recipient of a research fellowship from the National Kidney Foundation of New York and New Jersey.
-
↵2 To whom requests for reprints should be addressed, at Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
- Received June 24, 1991.
- Accepted April 7, 1992.
- ©1992 American Association for Cancer Research.
Volume 52, Issue 12
