DIFFERENTIAL EXPRESSION OF PROTEIN-KINASE-C ISOFORMS IN HUMAN COLORECTAL CANCERS

Protein kinase C (PKC), a serine/threonine kinase central to signal tr ansduction, is implicated in tumor promotion. At present, 10 PKC isofo rms have been cloned but their precise tissue-specific role has yet to be defined. In order to determine if PKC is reduced in colorectal can cers (CRC) and if specific PKC isoforms are altered in different stage s of human CRC progression, total RNA was extracted from human primary CRC, liver metastases, paired normal mucosa, and liver as well as CRC cell lines and examined for specific PKC isoform mRNA expression. PKC -alpha, beta II, delta, epsilon, eta(L), theta and xi were expressed i n all tissues examined, while PKC-beta I was not detected. PKC-alpha, beta II, delta, epsilon, and xi were decreased in most primary CRC. Ho wever, the reduction in PKC-beta II was greatest in advanced primary C RC (P < 0.05). Although PKC-gamma was detected in about 29.6% of prima ry CRC and liver metastases, it was absent from all corresponding norm al tissue. In addition, a second band hybridizing to our PKC-gamma pro be was uniquely present only in cancerous tissue and not in brain cont rol, suggestive of alternative splicing. PKC-alpha, delta, and epsilon , and xi were present in all cell lines. PKC-beta I/II were both unifo rmly absent from all cell lines. Since mRNA expression for most PKC is oforms is decreased in CRC, the previously reported decreases in overa ll PKC activity in CRC are not solely due to a post-translational enzy me modification. Since certain PKC isoforms were expressed uniquely di fferent in CRC relative to normal colonic mucosa, our results suggest that specific PKC isoforms may be involved in human CRC progression. ( C) 1995 Academic Press, Inc.