Changes in protein kinase C alpha, delta and in nuclear beta isoform expression in tumour and lung metastatic nodules induced by diethylnitrosamine in the rat.
PKC, a family of 11 related isoforms, appears deeply implicated in carcinogenesis and in the metastatic process, however, little being known on the specific role of each isoform in that process. In this work we analysed the subcellular distribution and the in situ expression of classical PKC (alpha and beta) isoforms and the expression of PKC delta in the tumour and lung-metastases induced in the rat using the 'resistant hepatocyte' model of diethylnitrosamine-induced hepatocarcinogenesis. With respect to control untreated liver, an activation and increased expression of PKC alpha was observed in tumour and lung metastatic nodules, while cytosolic and membrane PKC beta was undetectable. In contrast, nuclear PKC beta showed an increased activity in the tumour and a marked increased activity and expression in metastatic nodules, suggesting a possible role of such isoform in the metastatic process. The analysis of PKC delta expression revealed a down regulation in both tissues with respect to control untreated liver, suggesting the inhibitory role of such isoform on tumour cell proliferation in agreement with our previous observations. Taken together, these results point to a different role for PKC alpha and delta in the development of tumour and metastatic nodules using the 'resistant hepatocyte' model of liver carcinogenesis, and suggest a possible involvement of nuclear PKC beta in the development of secondary tumours.
La Porta
C A
CA
Department of General Physiology and Biochemistry, University of Milan, Italy.
Tessitore
L
L
Comolli
R
R
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002273:Carcinogens; D002467:Cell Nucleus / Q000201:enzymology*; D004052:Diethylnitrosamine; D007527:Isoenzymes / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000556:secondary; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D015820:Cadherins; D002273:Carcinogens; D007527:Isoenzymes; D004052:Diethylnitrosamine; D011493:Protein Kinase C