摘要
目的:探讨乳腺癌中雌激素受体与细胞信号传导通路MAPK上游激酶MEK-2和下游激酶p-ERK的作用机制。方法:应用雌激素(雌二醇)与雌激素受体拮抗剂(三苯氧胺)诱导BCML-TA299小鼠原位移植乳腺癌组织,通过病理形态学、免疫组织化学法检测ERβ、MEK-2和p-ERK的表达。结果:雌二醇(E2)促进细胞增殖,核分裂多见,肿瘤有丰富的血管,第20天时肺组织中血管腔及心腔内可见大量瘤栓。E2可激活MEK-2,p-ERK明显上调,ERβ与其基因有协同作用;而三苯氧胺(TAM)抑制细胞增殖,癌细胞明显受到损伤,核碎裂、凋亡小体多见,可见多灶性变性坏死区。同时出现ERβ、MEK-2和p-ERK下调,亦有协同作用。三苯氧胺与环磷酰胺联合应用效应优于单药的应用(F=211.88,F=179.08,F=156.44;P<0.05)。结论:ERβ与MAPK信号途径中上游激酶MEK-2和下游激酶p-ERK关系密切,并有协同作用,是乳腺癌发展中重要的调节信号。
Objective: To investigate the effect of estrogen and estrogen antagonist on the upstream kinase MEK-2 and the downstream kinase p-ERK in the MAPK signal transduction pathway in breast cancer. Methods: Estrogen (E2) and estrogen antagonist (TAM) were given to induce breast cancer tissue formation in BCML-TA299 mice after in situ transplantation, and thera the expression of ERβ, MEK-2 and p-ERK was detected by pathomorphology and immunohistochemistry. Results: E2 promoted cell proliferation. There was more karyokinesis anti redundant blood vessels in tumor tissues, especially those found in the lung. Many tumor emboli were seen in the heart chamber. TAM suppressed cell proliferation. Cancer cells treated with TAM were seriously danmged and displayed nnclear fragmentation, apoptotic bod- ies, focal degeneration and necrotic regions. Simuhaneously, the expression of ERI3, MEK-2 and p-ERK were downregulated. Combined application of TAM and CTX achieved better resuhs (F=211.88, F=179.08, F=156.44, P〈0.05). Conclusion: There is a close relationship between ERβ, MEK-2 and p-ERK. These signaling pathway prnteins act synergistically in breast cancer development.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2008年第4期219-223,共5页
Chinese Journal of Clinical Oncology
基金
天津市科委科研基金资助(编号:993605611)