PI3K-AKT signaling is a downstream effector of retinoid prevention of murine basal cell carcinogenesis

Po Lin So, Grace Y. Wang, Kevin Wang, Mindy Chuang, Venice Calinisan Chiueh, Paraic A. Kenny, Ervin H. Epstein

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7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-417
Number of pages11
JournalCancer Prevention Research
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

So, P. L., Wang, G. Y., Wang, K., Chuang, M., Chiueh, V. C., Kenny, P. A., & Epstein, E. H. (2014). PI3K-AKT signaling is a downstream effector of retinoid prevention of murine basal cell carcinogenesis. Cancer Prevention Research, 7(4), 407-417. https://doi.org/10.1158/1940-6207.CAPR-13-0304