肺癌雌激素受体表达与三苯氧胺拮抗治疗的研究

A study on the expression of estrogen receptor and the effect of Tamoxifen treatment in lung cancer

目的 在DNA分子水平上探讨雌激素受体 (ER)表达与肺癌生物学行为的关系及内分泌治疗的价值。方法 用单克隆抗体免疫组化染色 (SP)法检测 4 0例肺癌组织的ER表达 ,分析其临床病理特征和流式细胞仪分析DNA的含量。用逆转录多聚酶链式反应 (RT PCR)测定肺腺癌细胞株LTEP a 2的ER mRNA表达 ,分别在去激素培养条件下观察不同浓度的三苯氧胺 (Tamoxifen ,Tam)和雌二醇 (E2 )对其生长速度、细胞生长周期的影响。结果 肺癌ER阳性率为 5 7 5 %。ER表达与病理类型和组织学分级有关 ,而与肿块直径和临床分期无关。ER阳性者DNA含量低于ER阴性者 (P <0 0 1)。有ER mRNA表达的LTEP a 2肺癌细胞株在去激素环境下 ,低浓度E2 (10 -8M)可促进其生长。高浓度E2 (10 -6M )可抑制细胞生长 ,Tam (10 -6M)可抑制E2 (10 -8M )的生长刺激作用。结论 ER在分化程度较好的肺癌组织 ,特别是非小细胞肺癌中呈高表达趋势。雌激素与肺癌的发生、发展密切相关。

Objective To explore the relationship between the biological behavior of lung cancer and the expression of estrogen receptor in DNA levels and the value of endocrine treatment in lung cancer.Methods Monoclonal antibodies for the immunohistochemical strain assay (sp) of ER were used in 40 specimens of lung cancer.We investigated the clinical appearances of the patients and the pathological features of these samples.Changes in DNA quantity were detected by flow cytometry(FCM).RT PCR was applied in detecting the mRNA of ER in human lung cancer cell strains LTEP a 2.DCC(Dextran treated charcoal)treated fetal bovine serum was used.17β Estradiol and Tamoxifen were added in different concentrations into plates.Cell numbers and cell cycle were studied with cell counting and FCM.Results The positive rate of ER in lung cancer cells were 57 5%.The expression of ER was related to histopathologic grade and the pathological classification of lung cancer cells,but not related to the size of tumor and clinical stages.We found the DNA index of ER(+) lung cancer cells was lower than the ER(-) ones( P< 0 01).LTEP a 2 expressed ER mRNA in estrogen stripped medium,estradiol stimulated the growth of the cell below the concentration of 10 -7 M.Estradiol at the concentration of 10 -6 M could inhibit the growth of the cell.Tamoxifen(10 -6 M) could inhibit the stimulation of Estradiol(10 -8 M).Conclusions ER seems to be more highly expressed in well differentiated lung cancer cells and this trend is more significant in NSCLC.Estrogen is related to the development of lung cancer.Tamoxifen can inhibit the growth of lung cancer cells.