Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study.

Abstract

Protein kinase C delta (PKC-delta) protein levels are frequently low in chemically and UV-induced mouse skin tumors as well as in human cutaneous squamous cell carcinomas (SCCs). Furthermore, overexpression of PKC-delta in human SCC lines and mouse epidermis is sufficient to induce apoptosis and suppress tumorigenicity, making PKC-delta a potential tumor suppressor gene for SCCs. Here we report that PKC-delta is lost in human SCCs at the transcriptional level. We used laser capture microdissection to isolate cells from three normal human epidermis and 14 human SCCs with low PKC-delta protein. Analysis by quantitative reverse transcription-PCR revealed that PKC-delta RNA was reduced an average of 90% in the SCCs tested, consistent with PKC-delta down-regulation at the protein level. Analysis of DNA from nine of the same tumors revealed that PKC-delta gene was deleted in only one tumor. In addition, Ras-transformed human keratinocytes, which have selective down-regulation of PKC-delta at both protein and mRNA levels, had significantly repressed human PKC-delta promoter activity. Together, these results indicate that PKC-delta gene expression is suppressed in human SCCs, probably via transcription repression. Our results have implications for the development of topical therapeutic strategies to trigger the re-expression of pro-apoptotic PKC-delta to induce apoptosis in SCCs.

• Authors: Vipin Yadav, Nicole C Yanez, Sarah E Fenton, Mitchell F Denning
• Journal: The American journal of pathology (Am J Pathol) Vol. 176 Issue 3 Pg. 1091-6 (Mar 2010) ISSN: 1525-2191 [Electronic] United States
• PMID: 20093486 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• RNA, Messenger
• RNA, Neoplasm
• Protein Kinase C-delta

Topics

• Animals
• Carcinoma, Squamous Cell (enzymology, genetics, pathology)
• Cell Transformation, Neoplastic (genetics, pathology)
• Gene Deletion
• Gene Expression Regulation, Neoplastic
• Genes, ras
• Humans
• Keratinocytes (enzymology, pathology)
• Lasers
• Mice
• Microdissection
• Protein Kinase C-delta (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Skin Neoplasms (enzymology, genetics)