Bergh J, Björk P, Westlin J E, Nilsson S
Department of Oncology, Akademiska sjukhuset, University of Uppsala, Sweden.
Cancer Res. 1988 Aug 15;48(16):4615-9.
Estramustine-binding protein has previously been demonstrated in normal rat prostatic tissue, in normal human prostate epithelium, and in prostatic carcinomas. It binds specifically estramustine and estromustine, the cytotoxic metabolites of estramustine phosphate (Estracyt), a drug which is used in the treatment of prostatic carcinoma. In this study we have examined the presence of an estramustine-binding associated protein in a panel of human cell lines, representing the major histopathological types of lung cancer. A mouse (murine) monoclonal antiserum developed against rat estramustine-binding protein was used for immunohistochemical detection. Fast protein liquid chromatography was used for biochemical characterization. As judged from the immunohistochemical investigation, estramustine-binding protein was present in large amounts in five of six non-small cell carcinoma cell lines, while seven of eight small cell carcinoma cell lines were essentially negative. Fast protein liquid chromatography analyses of lysated cells from the lung cancer cell lines, incubated with [3H]estromustine, concurred with the results from the immunohistochemical stainings. These data strongly indicate a convincing connection between the immunoreactivity and ligand-binding properties of estramustine-binding protein in the cell lines examined. The presence of an estramustine-binding associated protein in human lung cancer cell lines has implications for further investigations into the biological relevance and the potential for eventual therapeutic applications.
雌莫司汀结合蛋白此前已在正常大鼠前列腺组织、正常人前列腺上皮以及前列腺癌中得到证实。它能特异性结合雌莫司汀和磷酸雌莫司汀的细胞毒性代谢产物雌二醇氮芥磷酸酯(癌腺治),该药物用于治疗前列腺癌。在本研究中,我们检测了一组代表肺癌主要组织病理学类型的人类细胞系中与雌莫司汀结合相关蛋白的存在情况。使用针对大鼠雌莫司汀结合蛋白产生的小鼠(鼠源)单克隆抗血清进行免疫组织化学检测。采用快速蛋白质液相色谱法进行生化特性分析。从免疫组织化学研究判断,在六个非小细胞癌细胞系中的五个中大量存在雌莫司汀结合蛋白,而八个小细胞癌细胞系中的七个基本呈阴性。对与[³H]雌二醇氮芥孵育的肺癌细胞系裂解细胞进行的快速蛋白质液相色谱分析结果与免疫组织化学染色结果一致。这些数据有力地表明在所检测的细胞系中,雌莫司汀结合蛋白的免疫反应性和配体结合特性之间存在令人信服的联系。人类肺癌细胞系中存在与雌莫司汀结合相关蛋白,这对于进一步研究其生物学相关性以及最终治疗应用的潜力具有重要意义。