Abstract

BackgroundOne of the most frequently deleted genes in cancer is CDKN2A encoding p16. This protein is often overexpressed in senescent cells, while its suppression can bypass the oncogene-induced senescence to enable transformation and tumorigenesis. The roles of the protein p16 are recently being expanded from the cell cycle progression regulator to the cellular regulator interacting in several different pathways. Yet data on its liver and liver cells’ expression are inconclusive.MethodsThe expression of the p16 gene in liver and liver cells was determined by RT-qPCR and compared to its protein amounts by western blotting.Resultsp16 is expressed at low levels in the liver and rat hepatocytes. Its expression varies from none to the considerable levels in the examined hepatocellular carcinoma cell lines (FaO and HepG2) and in immortalized mouse hepatocytes. Such significant expression differences of an important cellular regulator warrant the need to closely examine the differences in biochemical pathways correlated with the p16 expression when using hepatocytes and hepatoma liver models.

Highlights

  • The cyclin-dependent kinase inhibitor 2A (CDKN2A) gene encodes two protein regulators of cell cycle regulatory pathways, the p16(INK4A or p16) and p14(ARF), which are encoded in alternative reading frames (Stone et al, 1995)

  • Expression of the p16 gene was determined in rat liver, hepatocytes and hepatocyte-derived cells (Fig. 1) and compared to the expression in HEK 293T cell line with reported p16 expression (Cui et al, 2015)

  • Low levels of p16 expression were detected in the liver and primary rat hepatocytes

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Summary

INTRODUCTION

The cyclin-dependent kinase inhibitor 2A (CDKN2A) gene encodes two protein regulators of cell cycle regulatory pathways, the p16(INK4A or p16) and p14(ARF), which are encoded in alternative reading frames (Stone et al, 1995). Protein p16 is a regulator of cellular homeostasis controlling growth, senescence, apoptosis and cellular differentiation It inhibits cell cycle progression through the cyclin-dependent kinase-4 and -6/retinoblastoma (CDK4/6/Rb) pathway (Tyagi et al, 2017). It is an inhibitor of a cyclin-dependent kinase-4 (CDK4) (Angelico et al, 2021) This inhibition maintains the retinoblastoma protein (pRb, a product from the Rb gene) in a hypo-phosphorylated state and prevents the cell cycle progression from G1 to S phase (Li, Poi & Tsai, 2011). Loss of p16 expression because of promoter methylation was reported in 40% of the investigated cell lines in one study (Murai et al, 2005) and it commonly occurs in hepatocellular carcinoma (HCC) (Lv et al, 2017). We describe the differences in p16 expression levels among liver, primary and immortalized hepatocytes and hepatoma cell lines and discuss the implications of expression differences of this potentially important regulator of several cellular pathways

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