Correlation Between Expression Of HSP And Abitily Of Invasion And Metastasis In Human Breast Cancer Cell Lines

Objectives:To investigate the correlation between expression of HSP and invasive and metastatic potential in human breast cancer cell. Methods: The highly metastatic human breast cancer cell lines MDA-MB-435s and MDA-MB-231 were used in this study. The effects of HSP90 inhibitor GA on the proliferation of breast cancer cell were explored by MTT colorimetry for obtaining their IC50. Adhesion of MDA-MB-435s and MDA-MB-231 to Matrigel was measured with MTT assay. The invasive and metastatic abilities of human breast cancer lines MDA-MB-231 and MDA-MB-435s in vitro were explored by transwell chamber. The expression of HSP27,HSP70,HSP90 in MDA-MB-231 and MDA-MB-435s cells was detected by RT-PCR and Western-blotting. Results: GA showed a time/dose-dependent growth inhibition effect on MDA-MB-435s and MDA-MB-231 cells, IC50 of GA to MDA-MB-435s cell was 32.08nM and IC50 of GA to MDA-MB-231 cell was 54.4nM,The dose of GA used to treat the breast cancer cell lines were half of its IC50,i.e,16nM and 27.2nM respectively. Before treatment with GA,the ability of invasion and metastasis in MDA-MB-435s and MDA-MB-231 cells had no difference(P﹥0.05). After treatment with GA the ability of invasion and metastasis in MDA-MB-435s and MDA-MB-231 cells were significantly difference. (P<0.01). After treatment with GA the ability of invasion and metastasis in MDA-MB-435s lower than MDA-MB-231 cells (P<0.01).Compared with untreated group,adhesion of MDA-MB-435s and MDA-MB-231 were lower.The invaded cell numbers in invasive and metastatic experiments of MDA-MB-435s cell lines untreated or treated with GA were 113.2±6.42,41.2±9.04;132.6±6.58,57.8±9.42 respectively, the invasive and metastatic abilities of treated group were lower than untreated group significantly(P<0.01).The invaded cell numbers in invasive and metastatic experiments of MDA-MB-231 cell lines untreated or treated with GA were 120.4 ± 12.64 , 101.0 ± 5.24;140.4 ± 10.50 , 118.0 ± 11.73 respectively,the invasive and metastatic abilities of treated group were lower than untreated group significantly(P<0.05). The protein expression level of HSP90 in MDA-MB-435s was higher than MDA-MB-231 cell (P<0.01). The mRNA expression level of HSP90αin MDA-MB-435s was higher than MDA-MB-231 cell (P<0.01). The mRNA expression level of HSP90βhas no signifcant difference(P﹥0.05). The protein and mRNA expression level of HSP27 in MDA-MB-231 was higher than MDA-MB-435s cell (P<0.01). The protein expression level of HSP70 in MDA-MB-435s and MDA-MB-231 cells had no significant difference. (P ﹥ 0.05), The mRNA expression level of HSP70 in MDA-MB-231 was higher than MDA-MB-435s cell (P<0.05). Conclusion: The invasive and metastatic abilities of MDA-MB-435s and MDA-MB-231 cells were inhibited by HSP90 inhibitor GA.Consistent with HSP expression patterns in these two cell lines, MDA-MB-435s were inhibited more by GA than MDA-MB-231.Results had shown high expression of HSP90 in MDA-MB-435s and HSP27 in MDA-MB-231.It demonstrated that the HSP expression patterns were associated with the invasive and metastatic abilities of breast cancer lines.