摘要
目的:探讨雌激素受体β亚型(ERβ)和丝裂原活化蛋白激酶(MAPK)通路在乳腺癌发生、发展及凋亡过程中的作用及两者的相互作用机制。方法:将小鼠随机分为4组:对照组、三苯氧胺(TAM)组、环磷酰胺(CTX)组和联合组(TAM+CTX)。用免疫组化法联合检测给予三苯氧胺和环磷酰胺后小鼠乳腺癌(BCML-TA299)组织中ERβ、MEK-2和p-ERK的表达情况,用流式细胞仪检测各组肿瘤细胞的细胞周期和细胞凋亡的改变,并进行形态学方面的观察。结果:三苯氧胺和环磷酰胺均可抑制肿瘤生长,环磷酰胺组和联合组尤为明显(F=14.554,P<0.05);与对照组相比,其他三组肿瘤细胞增殖受到抑制,S期细胞百分比明显下降,均有统计学意义(P<0.05)。三苯氧胺组和联合组在G0期左侧出现凋亡峰,凋亡率分别为2.3%和13.1%,统计学上有差异(P<0.05);病理观察对照组肿瘤细胞生长活跃,呈侵袭性生长,核分裂象多见。其他各组肿瘤细胞呈不同程度的灶状坏死,细胞核肿胀变空,可见核固缩、核碎裂和凋亡小体,联合组尤为明显;三苯氧胺和环磷酰胺均可抑制ERβ、MEK-2和p-ERK的表达,与对照组相比有统计学差异(F=211.88、179.08、156.44,P<0.05),且各组中ERβ与MEK-2、p-ERK的表达有明显的协同作用。结论:ERβ和MAPK通路的相互作用共同影响乳腺癌的发展、凋亡及内分泌治疗耐药的发生,可能成为乳腺癌内分泌治疗和化学治疗的新靶点。
Objective： To investigate the mechanism of interaction between the ERβ and MAPK signal transduction pathways in the course of breast cancer development. Methods： Twenty-four mice were randomly divided into the control group, the TAM group, the CTX group or the combination group. Immunohistochemical staining was used to detect the expression level of ERβ, MEK-2 and p-ERK in breast cancer cells after the administration of TAM and CTX. Flow cytometry （FCM） was used to detect changes in cell cycle and the apoptotic index. Cell morphology was observed to detect transformation. Results： Both TAM and CTX inhibited tumor growth, especially in the CTX group and the combination group （F=14.554, P〈0.05）. In comparison with the control group, the other groups showed inhibition of tumor cell proliferation and a decreased percentage of cancer cells in S phase （P〈0.05）. FCM data showed the apoptotic peak was to the left of Go phase in the TAM group and the combination group. The apoptotic rate was 2.3% in the TAM group and 13.1% in the combination group （P〈0.05）. Tumor cells grew actively in the control group and karyokinesis was observed. Cancer cells showed various levels of focal necrosis in the experimental groups and the cell nuclei underwent swelling, cavitations,and karyopyknosis. Nuclear fragmentation and apoptotic bodies could be observed, especially in the combination group. Both TAM and CTX significantly inhibited the expression of ERβ, MEK-2 and p- ERK in breast cancer cells （F=211.88, 179.08, 156.44,P〈0.05）. The expression of these three proteins demonstrated synergistic actions. Conclusion： We demonstrate that the ERβ and MAPK signal transduction pathways interact and can influence cancer development, apoptosis and endocrine therapy resistance. These proteins may become new targets of endocrine and chemical therapies for breast cancer.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2007年第18期1053-1057,共5页
Chinese Journal of Clinical Oncology
基金
天津市科委科研基金资助(编号:993605611)
