Interferon-responsive protein kinase (p68) and proliferating cell nuclear antigen are inversely distributed in head and neck squamous cell carcinoma

Abstract

PKR (protein kinase, interferon-responsive) is a ribosomal-associated protein kinase found in all human cells. When activated by dsRNA or polyanionic substances, PKR efficiently inhibits cellular protein synthesis. PKR expression has been correlated with cellular differentiation in a number of tumor types, including squamous cell carcinoma of the head and neck region. Although transfection of PKR into mouse fibroblasts and yeast cells inhibits proliferation, it is not known if modulation of native PKR levels occurs during cellular proliferation and differentiation in human normal and neoplastic tissues. To determine whether PKR expression was inversely related to proliferative activity in vivo, we used double-label immunohistochemistry to colocalize PKR and the proliferation marker, proliferating cell nuclear antigen (PCNA), in a series of head and neck squamous cell carcinomas. Overall, neoplasms demonstrating high levels of PKR showed low levels of PCNA immunoreactivity; carcinomas with low levels of PKR expressed high levels of PCNA. Within individual tumors, PKR and PCNA showed an inverse regional distribution: PKR was located predominantly in the center of tumor nests, while PCNA was restricted to the periphery. Patients whose tumors expressed high levels of both PKR and PCNA had the longest mean disease-free survival. These findings support the hypothesis that PKR levels are modulated in cell proliferation and differentiation in head and neck squamous cell carcinoma. Further studies are needed to clarify the mechanisms underlying the antiproliferative activity of PKR.