J Korean Assoc Maxillofac Plast Reconstr Surg.  2001 Jul;23(4):295-305.

Expression of protein kinase C isoforms in chemical carcinogen-induced neoplastic transformation of human EPITHELIAL cells

• Byeon KJ
• Hong LW
• Kim CS

Abstract

Protein kinase C (PKC) is known to play a pivotal role in neoplastic transformation cells and its high expression is often found in a variety of types of tumors including oral cancer. While PKC is associated with the altered signal transduction pathway of the tumor cells, it is still unclear which isoform is involved in the carcinogenesis process. Since the cellular distributions and the roles of PKC are isoform-specific, it is very important to identify the specific target molecules to improve our understanding of the carcinogenesis processes. Thus, the present study attempted to perform chemical carcinogen-induced neoplastic transformation of human epithelial cells and analyze the specific isoform of PKCs involved in the cellular transformation. The study analyzed overall PKC responses upon MNNG(N-Methyl-N'-nitro-N-nitroso guanidine) exposure with [3H]PDBu binding assay. PKC translocation was observed at high doses of MNNG treatment in the presence of extracellular calcium. Such effects were not observed in the absence of extracellular calcium. Translocational effects with exposure of MNNG was further enhanced in the presence of hydrocortisone. The result suggests that the type of PKC involved may be Ca2+-dependent classical isoform and steroid hormone enhances PKC activation. Among cPKC isoforms examined, only PKC-alpha and r showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. PKC-epsilon in nPKC class showed an increased translocation, but other forms in this class did not show the effect. None of isoforms in aPKC class was affected by MNNG treatment. The study demonstrated that there was a certain specificity in the patterns of isoform induction follwong chemical carcinogen exposure and helped identify all the types of PKC isoforms expressed in human epithelial cells. It was revealed that PKC isoforms were activated in an early resonse to chemical carcinogen, suggesting that PKC be associated with carcinogenesis process from an early stage in this particular cell system. The study will contribute to improving our understanding of chemical-induced carcinogenesis in human cells and may provide a scientific basis to introduce the specific PKC inhibitors as an anticancer drug of epithelial cell-origin cancers including oral cancer.

Keyword

Protein kinase C; Isoforms; Carcinogenesis

MeSH Terms

Calcium
Carcinogenesis
Cytosol
Epithelial Cells*
Humans*
Hydrocortisone
Membranes
Methylnitronitrosoguanidine
Mouth Neoplasms
Protein Isoforms
Protein Kinase C*
Protein Kinases*
Sensitivity and Specificity
Signal Transduction
Calcium
Hydrocortisone
Methylnitronitrosoguanidine
Protein Isoforms
Protein Kinase C
Protein Kinases