Atlas I, Mendelsohn J, Baselga J, Fair W R, Masui H, Kumar R
Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1992 Jun 15;52(12):3335-9.
Findings of increased numbers of epidermal growth factor receptors (EGF-R) and increased expression of transforming growth factor alpha (TGF-alpha) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF-alpha 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 greater than 35% when cultured in the presence of TGF-alpha 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-alpha enhanced the levels of expression of EGF-R mRNA and TGF-alpha mRNA. In addition, incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF-alpha species in the culture medium. Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF-alpha and that this regulatory pathway can be interrupted using antibody to its receptor, EGF-R.
在人类肾细胞癌手术标本中发现表皮生长因子受体（EGF-R）数量增加以及转化生长因子α（TGF-α）表达增强，这使得人们提出这些肿瘤的生长可能受TGF-α以自分泌方式调节的观点。在本文所呈现的研究中，我们使用两种人类肾癌细胞系SKRC-4和SKRC-29检验了这一假说。我们证明，当在TGF-α或表皮生长因子（EGF）存在的情况下培养时，SKRC-4和SKRC-29细胞的生长均受到超过35%的刺激，而如果在抗EGF-R单克隆抗体225存在的情况下培养，其生长则受到29%至46%的抑制。用TGF-α处理细胞可增强EGF-R mRNA和TGF-α mRNA的表达水平。此外，用单克隆抗体225孵育细胞可显著提高培养基中分泌的TGF-α种类的水平。我们的研究结果表明，人类肾癌细胞的增殖可能受内源性产生的TGF-α调节，并且这种调节途径可以通过使用针对其受体EGF-R的抗体来阻断。
