Brysch W, Magal E, Louis J C, Kunst M, Klinger I, Schlingensiepen R, Schlingensiepen K H
Biognostik GmbH, Göttingen, Germany.
Cancer Gene Ther. 1994 Jun;1(2):99-105.
The c-erbB-2 proto-oncogene codes for a 185-kd putative growth factor receptor that is highly homologous to but distinct from the epidermal growth factor (EGF) receptor. Amplification and overexpression of c-erbB-2 occurs in a number of human tumors, in some of which it is a negative prognostic factor. This study investigates the possibility of inhibiting tumor-cell proliferation by blocking c-erbB-2 expression in the human mammary carcinoma cell line SK-Br-3 using chemically modified antisense oligodeoxynucleotides. Expression of the p185c-erbB-2 protein product was selectively reduced within 48 hours and resulted in a growth arrest of SK-Br-3 cells. Biochemical studies of tyrosine-kinase and S6-kinase activities after antisense inhibition of c-erbB-2 show that p185c-erbB-2 activates the S6-kinase signalling pathway in a nonlinear, dose-dependent manner. This may be relevant for the design of therapeutic strategies involving the inhibition of c-erbB-2 (proto)- oncogene expression.
c-erbB-2原癌基因编码一种185kd的假定生长因子受体，它与表皮生长因子（EGF）受体高度同源但又有所不同。c-erbB-2的扩增和过度表达在多种人类肿瘤中出现，其中一些肿瘤中它是一个负面预后因素。本研究探讨了使用化学修饰的反义寡脱氧核苷酸阻断人乳腺癌细胞系SK-Br-3中的c-erbB-2表达来抑制肿瘤细胞增殖的可能性。p185c-erbB-2蛋白产物的表达在48小时内被选择性降低，并导致SK-Br-3细胞生长停滞。对c-erbB-2进行反义抑制后对酪氨酸激酶和S6激酶活性的生化研究表明，p185c-erbB-2以非线性、剂量依赖性方式激活S6激酶信号通路。这可能与涉及抑制c-erbB-2（原）癌基因表达的治疗策略设计相关。
