The G2 phase arrest induced by sterigmatocystin is dependent on hMLH1- ERK/p38-p53 pathway in human esophageal epithelium cells in vitro

Abstract

Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G2 cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro. Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G2 phase arrest is still not clarified. In the present study, we first explored the role of MAPK pathway upon ST induced G2 arrest, and found that ST up-regulated the expression of G2/M regulatory factors through MAPK signaling pathway (both ERK and p38, but not JNK pathway). The inhibition of ERK and p38 significantly inhibited p53 activation by ST. Blockage of MMR pathway by silencing hMLH1 expression inhibited ERK, p38 and p53 activation and then attenuated G2 arrest by ST. Thus, in conclusion, the current study demonstrated that in response to ST induced DNA damage, hMLH1 was first activated, then triggered ERK, p38 and p53 activation and finally resulted in G2 arrest in HET-1A cells.