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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.

SUBMITTER: Yadav V

PROVIDER: S-EPMC2832131 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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

Yadav Vipin V Yanez Nicole C NC Fenton Sarah E SE Denning Mitchell F MF

The American journal of pathology 20100121 3

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 microdissecti ...[more]

PMID: 20093486

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Dataset Information

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

Publications

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

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