Role and significance of histone acetylation in proliferation of breast cancer cell line MCF-7 induced by estrogen

Abstract:

Objective：To investigate the role and significance of histone acetylation in proliferation of breast cancer cell line MCF-7 induced by estrogen. Methods：Human breast cancer MCF-7 cells were used as the research object. Effect of 17β-estradiol（１７β-E2）on proliferation of MCF-7 cells was investigated with CCK-8 assay and the optimal concentration of 17β-E2 in the following experi－ment was determined according to the proliferation rate. Effect of Garcinol on proliferation of MCF-7 cells by 17β-E2 was investigat－ed with CCK-8 assay and the intermediate concentration of Garcinol in the following experiment was determined according to the in－hibition rate. Cell cycle and apoptosis were analyzed by flow cytometry. Expression of acetylated histone 3（ac-H3），acetylated histone ４（ac-H4） protein was determined by Western blot. CyclinD1 mRNA，B cell lymphoma/leukemia-2（Bcl-2） mRNA，B cell lymphoma/leukemia-xl（Bcl-xl） mRAN expression in MCF -7 cells was measured by RT-PCR and expression of CyclinD1，Bcl-2，Bcl-xl protein was determined by Western blot. Results：Proliferation of MCF-7 cells treated with 17β-E2 was inhibited by acetyltransferase inhibitor Garcinol and transformation of MCF-7 cell cycle was arrested at G0/G1 phase and rate of apoptosis was increased（P=0.000）. Expres－sion level of ac-H3，ac-H4 protein in MCF-7 cells treated with 17β-E2 was increased（P=0.007，P=0.013），in which ac-H3 was inhib－ited by Garcinol（P=0.006） but no ac-H4（P=0.347）. Correspondingly，17β-E2 promoted the mRNA transcription（P=0.007，P=0.044，P=0.007） and protein expression（P=0.000，P=0.002，P=0.000） levels of CyclinD1，Bcl-2，Bcl-xl in MCF-7 cells，which were also in－hibited by Garcinol（P=0.001，P=0.017，P=0.002，P=0.000，P=0.001，P=0.001）. Conclusions：17β-E2 promoting proliferation and inhibiting apoptosis of human breast cancer MCF-7 cells is related with elevated acetylation level of histone. Garcinol plays an inhibitive role in 17β-E2 promoting proliferation of MCF-7 cells.