Epidermal Growth Factor Signaling Regulates the Expression of Metastasis Tumor Antigen 1 in Mouse Pachytene Spermatocyte

Abstract

Selective regulation of gene transcription is clearly important for cells to orchestrate an adaptive response to heat stress. We previously showed that Metastasis Associated Protein 1 (MTA1), a component of the nucleosome remodeling and deacetylase (NuRD) complex, operates as a negative coregulator of p53 in the maintenance of the apoptotic balance in pachytene spermatocytes (PS) after heat stress, although specific mechanisms are not well defined. The purpose of the current study was to investigate potential upstream signaling events activating MTA1 pathway in murine PS. Using murine sialoadenectomy model, it was demonstrated that deprivation of circulated EGF significantly impaired the in vivo expression of MTA1 in the PS. The upstream regulation of MTA1 expression during meiosis by endogenous EGF was further confirmed in vitro using a selective Epidermal Growth Factor Receptor (EGFR) inhibitor, tryphostin AG1478. Moreover, inhibition of EGF signaling by AG1478 treatment significantly suppressed the heat stress-induced MTA1 in PS. The available data collectively suggest that EGF signaling regulates the expression of MTA1 in PS, and early activation of EGF/MTA1 cascade in PS in response to heat stress may serve as an intrinsic self-defensive mechanism maintaining apoptotic balance during meiotic heat stress.