Yaqi Wang^1,, Shunli Zhang¹, Jie Ma¹, Hong Wang¹, Nan Jiang¹, Yang Wang¹, Jun Zhang², Zhuo Wang², Jinghua Zhang^3,

Ras signal regulates the pathway activity through the extracellular signal regulated kinase (ERK1/2) phosphorylation, Ras mutations or abnormal activation will lead to cancer. In order to study the effects on MCF-7 breast cancer cells proliferation and migration when histone H4K16 acetylating (H4K16ac) in activated Ras signaling pathway, we did a series of experiments. Western blot was used to detect the expression level of ERK1/2, p-ERK1/2, H4 and H4K16ac in different transfected groups. Immunohistochemical technique was used to detect the levels of p-ERK1/2 and H4K16ac in breast cancer tissues and adjacent tissues. The mutant plasmids were constructed to activate cellular Ras signaling pathway and to simulate intracellular H4K16ac. The proliferation ability of cells was detected by CCK-8 technology, and the migration ability of cells was detected by Transwell. In the control group, the activated Ras signal group, and the simulated H4K16ac group, the relative expression levels of p-ERK1/2 were 0.285±0.017, 0.407±0.026, 0.373±0.028; the relative expression levels of H4K16ac were 0.331±0.013, 0.082±0.005, 0.082±0.007. The expression of p-ERK1/2 in breast cancer tissue and adjacent tissue was 0.064±0.001 and 0.051±0.001, respectively; the expression of H4K16ac was 0.028±0.003 and 0.063±0.005, respectively. The proliferation and migration of cancer cells increased by 34.8% and 103.1% respectively (p<0.05), when the Ras signaling pathway was activated. Compared with the cancer cells activated Ras signal pathway, the proliferation and migration of cells simulated H4K16ac were decreased by 25.1% and 42.7% respectively (p<0.05). We demonstrated that after the Ras signal pathway was activated, the expression level of p-ERK1/2 rose, resulting in the decrease of H4K16ac. The increase of H4K16ac will inhibit the Ras signaling pathway activity, thus inhibit proliferation and migration of breast cancer cells. H4K16ac plays an important role in proliferation and migration from breast cancer tissues to normal breast tissues.

breast cancer, H4K16ac, Ras, migration, proliferation