Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study.
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.
Yadav
Vipin
V
Molecular Biology Program, Cardinal Bernardin Cancer Center, the Stritch School of Medicine, Department of Pathology, Room 304, Loyola University Medical Center, 2160 S First Avenue, Maywood, IL 60153, USA.
Yanez
Nicole C
NC
Fenton
Sarah E
SE
Denning
Mitchell F
MF
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D007834:Lasers; D051379:Mice; D042282:Microdissection; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051745:Protein Kinase C-delta