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

Protein kinase C (PKC), a serine/threonine kinase central to signal transduction, is implicated in tumor promotion. At present, 10 PKC isoforms have been cloned but their precise tissue-specific role has yet to be defined. In order to determine if PKC is reduced in colorectal cancers (CRC) and if specific PKC isoforms are altered in different stages 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 in all tissues examined, while PKC-beta I was not detected. PKC-alpha, beta II, delta, epsilon, and xi were decreased in most primary CRC. However, the reduction in PKC-beta II was greatest in advanced primary CRC (P < 0.05). Although PKC-gamma was detected in about 29.6% of primary CRC and liver metastases, it was absent from all corresponding normal tissue. In addition, a second band hybridizing to our PKC-gamma probe was uniquely present only in cancerous tissue and not in brain control, suggestive of alternative splicing. PKC-alpha, delta, and epsilon, and xi were present in all cell lines. PKC-beta I/II were both uniformly absent from all cell lines. Since mRNA expression for most PKC isoforms is decreased in CRC, the previously reported decreases in overall PKC activity in CRC are not solely due to a post-translational enzyme modification. Since certain PKC isoforms were expressed uniquely different 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.