Molecular Signaling Pathways in Human Skin Carcinogenesis

The delta isoform of Protein Kinase C (PKC- ) is a potential tumor suppressor gene for human squamous cell carcinomas (SCCs). The objective of this study is to investigate the mechanism of PKC- loss in human SCCs. We used Laser Capture Microdissection to isolate cells for nucleic acid analysis from normal epidermises and human SCCs. Using this approach, we found that PKC- is lost at the mRNA level in human SCCs, and that the PKC- gene is rarely deleted suggesting that the mechanism of down-regulation of PKC- in SCCs is at the level of gene transcription. Further investigation identified a novel Ras PI3K Fyn NF- B signaling pathway necessary and suffcicient for PKC- repression in human keratinocytes. Our results have implications for the development of therapeutic strategies abrogating this signaling pathway to trigger the re-expression of pro-apoptotic PKC- to induce apoptosis in SCCs.

Autorentext

Dr. Vipin Yadav was born in Jan. 1983 at Agra, India to GpCpt. Rajendra Singh and Smt. Pushpa Yadav. He holds a B.Tech degree in Biotechnology from Anna University, India (2000) and a Ph.D. in Molecular Biology from Loyola University Chicago, USA (2010). In 2011, he joined Eli Lilly and Company as a Post-Doctoral Scientist to study cancer biology.

Klappentext

The delta isoform of Protein Kinase C (PKC-d) is a potential tumor suppressor gene for human squamous cell carcinomas (SCCs). The objective of this study is to investigate the mechanism of PKC-d loss in human SCCs. We used Laser Capture Microdissection to isolate cells for nucleic acid analysis from normal epidermises and human SCCs. Using this approach, we found that PKC-d is lost at the mRNA level in human SCCs, and that the PKC-d gene is rarely deleted suggesting that the mechanism of down-regulation of PKC-d in SCCs is at the level of gene transcription. Further investigation identified a novel Ras PI3K Fyn NF- B signaling pathway necessary and suffcicient for PKC-d repression in human keratinocytes. Our results have implications for the development of therapeutic strategies abrogating this signaling pathway to trigger the re-expression of pro-apoptotic PKC-d to induce apoptosis in SCCs.