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阿霉素对多瘤病毒MT抗原转化细胞中pp60c-src激酶活性的影响。

Effects of doxorubicin on pp60c-src kinase activity in polyoma virus MT antigen transformed cells.

作者信息

Yang Y W, Chang Y H

机构信息

School of Pharmacy, College of Medicine, National Taiwan University, Taipei.

出版信息

Anticancer Res. 1994 Nov-Dec;14(6B):2529-35.

PMID:7532928
Abstract

Interaction between polyoma virus (Py) encoded middle tumor antigen (MTAg) and the cellular src gene product, pp60c-src, has been shown to be correlated with the enhancement of pp60c-src kinase activity and the transforming ability of the virus. In the present study, FR3T3 cells were transfected with plasmids encoding MTAg and used to study the effects of the antineoplastic agent, doxorubicin (DOX), on pp60c-src kinase activity. Our results showed that transfection of FR3T3 cells with MTAg results in relatively high levels of MTAg expression and enhancement of pp60c-src kinase activity several folds over that observed in the control cells. Treatment of the transformed MTF4 cells with DOX up to 5 x 10(-6) M was shown to have no effect on the in vitro phosphorylation of MTAg and pp60c-src in the drug-treated cell lysates. On the contrary, treatment of src immunocomplexes with DOX resulted in a reduction in kinase activity. The inhibition appears to be a dose-dependent competition with respect to ATP concentrations.

摘要

多瘤病毒(Py)编码的中间肿瘤抗原(MTAg)与细胞src基因产物pp60c-src之间的相互作用已被证明与pp60c-src激酶活性的增强以及病毒的转化能力相关。在本研究中,用编码MTAg的质粒转染FR3T3细胞,并用于研究抗肿瘤药物阿霉素(DOX)对pp60c-src激酶活性的影响。我们的结果表明,用MTAg转染FR3T3细胞会导致MTAg表达水平相对较高,且pp60c-src激酶活性比对照细胞中观察到的增强了几倍。用高达5×10⁻⁶ M的DOX处理转化的MTF4细胞,结果显示对药物处理的细胞裂解物中MTAg和pp60c-src的体外磷酸化没有影响。相反,用DOX处理src免疫复合物会导致激酶活性降低。这种抑制似乎是关于ATP浓度的剂量依赖性竞争。

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