Objective: 

EGF and androgen signaling pathways are crucial for cell cycle regulation, differentiation and survival in prostate epithelium. Since, AKT is a major survival pathway and is influenced via EGFR signaling, determines the androgen receptor transactivation in prostate cells. Therefore, many researches have shown that the deregulation of AKT signaling is a decisive step for prostate carcinogenesis. HN1 is a ubiquitously expressed gene and encodes an evolutionary conserved, but an uncharacterized small protein.

Methods: 

In this study, how HN1 influenced by EGF and androgen treatments were investigated using androgen responsive cell line LNCaP. The effects of HN1 on AKT-GSK3B phosphorylations and consequently B-Catenin stabilization were investigated using silencing and overexpression approaches involving flow cytometry, western blotting and immunofluorescein techniques.

Results: 

As a result, we have shown that EGF and androgen regulate HN1 in AKT dependent manner, and HN1 knockdown results an increase in AKT activation. Further, subsequent GSK3B phospho-inhibition results with partial stabilization of B-catenin, which was evidenced as increases in c-myc and cyclin D1 expressions, and nuclear accumulation of cyclin D1. Moreover, HN1 overexpression also influences androgen signaling and alters the cell morphology by E-cadherin association of B-catenin. Thus, HN1 is a ubiquitously expressed gene; its expression is tightly regulated with multiple signaling pathways and it is required for cellular morphogenesis.

Conclusions: 

HN1 is a hormone/growth factor regulated gene and it has important roles in AKT dependent GSK3B signaling, regulates cell division, nucleus morphology and cytoskeletal protein expressions.