Molecular characterization of mutations in patients with benign and aggressive recurrent respiratory papillomatosis: a preliminary study.

This study was performed to determine whether genetic polymorphisms within the human papillomavirus (HPV) can predict the disease course in patients with recurrent respiratory papillomatosis. The HPV type and genomic variations were determined by comparing the sample sequence to a prototypical HPV in the database of the National Center for Biotechnology Information. The results were correlated with the clinical course. Seven children and 6 adults were studied. Six of the 7 children had aggressive disease associated with HPV type 11. The remaining child had HPV type 6. Five of the 6 adult patients had HPV type 6; 1 had a history of juvenile recurrent respiratory papillomatosis. The remaining adult had an aggressive disease course associated with HPV type 11. The HPV type and specific polymorphisms were conserved over time in serial isolates. The age of onset and medical therapy did not appear to affect the polymorphisms present. Future studies may find that the presence of certain polymorphisms is associated with different geographic locations and possibly with the disease course.

Protein kinase C betaII and PKCiota/lambda: collaborating partners in colon cancer promotion and progression.

We previously showed that elevated expression of either protein kinase CbetaII (PKCbetaII) or PKCiota/lambda enhances colon carcinogenesis in mice. Here, we use novel bitransgenic mice to determine the relative importance of PKCbetaII and PKCiota/lambda in colon carcinogenesis in two complimentary models of colon cancer in vivo. Bitransgenic mice overexpressing PKCbetaII and constitutively active PKCiota (PKCbetaII/caPKCiota) or kinase-deficient, dominant-negative PKCiota (PKCbetaII/kdPKCiota) in the colon exhibit a similar increase in colon tumor incidence, tumor size, and tumor burden in response to azoxymethane (AOM) when compared with nontransgenic littermates. However, PKCbetaII/kdPKCiota mice develop predominantly benign colonic adenomas, whereas PKCbetaII/caPKCiota mice develop malignant carcinomas. In contrast, PKCbeta-deficient (PKCbeta(-/-)) mice fail to develop tumors even in the presence of caPKCiota. Our previous data indicated that PKCbetaII drives tumorigenesis and proliferation by activating beta-catenin/Apc signaling. Consistent with this conclusion, genetic deletion of PKCbeta has no effect on spontaneous tumorigenesis in Apc(min/+) mice. In contrast, tissue-specific knockout of PKClambda significantly suppresses intestinal tumor formation in Apc(min/+) mice. Our data show that PKCbetaII and PKCiota/lambda serve distinct, nonoverlapping functions in colon carcinogenesis. PKCbetaII is required for AOM-induced tumorigenesis but is dispensable for tumor formation in Apc(Min/+) mice. PKCiota/lambda promotes tumor progression in both AOM- and Apc(min/+)-induced tumorigenesis. Thus, PKCbetaII and PKCiota, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively.