不同HER-2表达水平对乳腺癌细胞生物学行为的影响

背景与目的:人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)属于受体酪氨酸激酶中的生长因子受体家族,其表达差异在乳腺癌靶向药物的临床使用中起决定作用.该研究旨在筛选出HER-2不同表达水平的乳腺癌细胞株,研究HER-2表达差异对肿瘤细胞生物学行为的影响.方法:对乳腺癌细胞系SK-BR-3进行克隆纯化,利用德国西门子公司ADVIA Centuar CP系统电化学发光技术检测细胞培养上清液中可溶性HER-2(soluble HER-2,sHER-2)的表达水平,筛选出sHER-2高表达细胞株(大于50.0 ng/mL)、中表达细胞株(15.8~50.0 ng/mL)及低表达细胞株(小于15.8 ng/mL).通过细胞培养观察以上3种乳腺癌细胞株的形态学变化,并通过一系列体外实验比较细胞的生物学特性,包括克隆形成实验、划痕实验和Transwell检测等.结果:与正常乳腺上皮细胞相比,乳腺癌细胞系SK-BR-3表达的sHER-2水平明显增高.其中,sHER-2高表达细胞株的克隆形成率为(51.3±3.4)%,明显高于中表达细胞株[(42.0±3.7)%]和低表达细胞株[(26.7±2.9)%];sHER-2高表达细胞株的迁移率为(50.0%±0.6)%,明显高于sHER-2中表达细胞株[(19.5±3.4)%]和sHER-2低表达细胞株[(13.6±1.0)%];sHER-2高表达细胞株的侵袭能力为(53.5±4.2)%也明显比sHER-2中表达细胞株[(33.2±3.9)%]和低表达细胞株[(28.9±5.4)%]细胞株强,差异均有统计学意义(P<0.05).结论:乳腺癌sHER-2高表达细胞株具有促增殖、促细胞动力等生物学效应,因此能为临床合理使用乳腺癌靶向药物提供参考依据.

The effect of different expression levels of HER-2 on the biological characteristics of breast cancer cells

Background and purpose: Human epidermal growth factor receptor 2 (HER-2) is the member of tyrosine kinase receptor family. Its differential expression plays the key role in choosing targeted drug for breast cancer. This study focused on screening the breast cancer cell clones of different HER-2 expression levels, and studying the bi-ological characteristics of these cells. Methods: Breast cancer SK-BR-3 cells were clonally purified, and the expression level of soluble HER-2 (sHER-2) from the culture supernatant was detected by the ECLIA on ADVIA Centaur CP System. Cell clones with high expression (>50.0 ng/mL), medium expression (15.8-50.0 ng/mL) and low expression (<15.8 ng/mL) of sHER-2 were identified, respectively. This study observed the morphological changes of cell strains with differential expression levels of sHER-2 by cell culture. Besides, biological characteristics were compared by a series of experiments in vitro, such as clone formation, scratch assay, and transwell detection. Results: Compared with normal breast cells, sHER-2 was overexpressed significantly in SK-BR-3 breast cancer cells. Furthermore, the abilities of clone formation, mobility and invasion of sHER-2 high expression cell strain [(51.3±3.4)%, (50.0±0.6)% and (53.5±4.2)%] were signifi-cantly higher than those of sHER-2 medium expression [(42.0±3.7)%, (19.5±3.4)% and (33.2±3.9)%] or sHER-2 low expression [(26.7±2.9)%, (13.6±1.0)% and (28.9±5.4)%], and the differences were all statistically significant (P<0.05). Conclusion: Breast cancer cell strain with high expression level of sHER-2 can enhance cell proliferation, promote cell motility and other biological effects, which may lay the foundation for clinical screening of targeted drug therapies for breast cancer.