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Identification of mTOR inhibitor-resistant genes in cutaneous squamous cell carcinoma

Seong-Lan Yu1, Dong Chul Lee2, Seung Woo Baek3

  • 1Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea, jaeku@konyang.ac.kr.

Cancer Management and Research
|December 21, 2018
PubMed
Abstract

Insights

This study investigated genes linked to mTOR inhibitor resistance in skin squamous cell carcinoma (SCC). CCND1 gene overexpression was identified as a key factor, potentially guiding future therapeutic strategies for SCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • The PI3K/AKT/mTOR pathway is often activated in squamous cell carcinomas (SCCs).
  • mTOR inhibitors show promise for metastatic SCC in immunosuppressed patients, but their efficacy in non-immunosuppressed skin SCC is unproven.
  • The precise role of mTOR signaling in SCC remains unclear.

Purpose of the Study:

  • To identify genes associated with resistance to mTOR inhibitors in skin SCC.
  • To elucidate the mechanism of mTOR signaling in SCC.
  • To explore potential therapeutic targets for skin SCC.

Main Methods:

  • Cell viability assays and Western blotting were performed.
  • Global gene expression profiling using Affymetrix analysis on A431 and HSC-1 cells treated with everolimus.
  • Pathway analysis using Ingenuity Pathway Analysis (IPA) to identify gene networks related to everolimus resistance.

Main Results:

  • Everolimus demonstrated cytotoxic effects in HSC-1 cells but not A431 cells.
  • Phosphorylated mTOR (p-mTOR) levels decreased with increasing everolimus concentrations in HSC-1 cells.
  • Microarray analysis revealed genes including MYC, CCND1, TP73, NUPR1, SBD, ERBB2, and CDKN2B were linked to mTOR inhibitor resistance, with CCND1 overexpression being most significant.

Conclusions:

  • Key genes conferring resistance to mTOR inhibitors in skin SCC were identified.
  • These findings may aid in selecting appropriate therapeutic targets for skin SCC treatment.
Keywords:
CCND1 genegene profilingmTOR inhibitorsquamous cell carcinoma

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