PI3K-AKT signaling is a downstream effector of retinoid prevention of murine basal cell carcinogenesis
| Autor: | Grace Wang, Ervin H. Epstein, Mindy Chuang, Po-Lin So, Venice Calinisan Chiueh, Paraic A. Kenny, Kevin Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Skin Neoplasms medicine.drug_class Cell Apoptosis Biology Real-Time Polymerase Chain Reaction Article Mice Phosphatidylinositol 3-Kinases Retinoids Keratolytic Agents Tazarotene medicine Biomarkers Tumor Tumor Cells Cultured Animals Humans Retinoid RNA Messenger Enzyme Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Oligonucleotide Array Sequence Analysis Cell growth Reverse Transcriptase Polymerase Chain Reaction Nicotinic Acids Molecular biology Retinoic acid receptor medicine.anatomical_structure Cell Transformation Neoplastic Oncology Carcinoma Basal Cell Drug Resistance Neoplasm Cancer research Signal transduction Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Popis: | Basal cell carcinoma (BCC) is the most common human cancer. We have demonstrated previously that topical application of the retinoid prodrug tazarotene profoundly inhibits murine BCC carcinogenesis via retinoic acid receptor γ–mediated regulation of tumor cell transcription. Because topical retinoids can cause adverse cutaneous effects and because tumors can develop resistance to retinoids, we have investigated mechanisms downstream of tazarotene's antitumor effect in this model. Specifically we have used (i) global expression profiling to identify and (ii) functional cell-based assays to validate the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway as a downstream target pathway of tazarotene's action. Crucially, we have demonstrated that pharmacologic inhibition of this downstream pathway profoundly reduces murine BCC cell proliferation and tumorigenesis both in vitro and in vivo. These data identify PI3K/AKT/mTOR signaling as a highly attractive target for BCC chemoprevention and indicate more generally that this pathway may be, in some contexts, an important mediator of retinoid anticancer effects. Cancer Prev Res; 7(4); 407–17. ©2014 AACR. |
| Databáze: | OpenAIRE |
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