Human telomerase reverse transcriptase is a promising target for cancer inhibition in squamous cell carcinomas

Anticancer Res. 2014 Nov;34(11):6389-95.

Abstract

Background/aim: The present study aimed to investigate whether the down-regulation of human telomerase reverse transcriptase (hTERT) may induce an anti-invasive effect in oral squamous cell cancer cell lines.

Materials and methods: A genetically-engineered squamous carcinoma cell line overexpressing hTERT in immortalized oral keratinocytes transfected by human papilloma virus (HPV)-16 E6/E7 (IHOK) was used. In vivo tumorigenicity was examined using an orthotopic xenograft model of nude mice. For evaluating anti-invasive activity by knockdown of hTERT expression, transwell invasion assay and real-time polymerase chain reaction (PCR) for matrix metalloproteinases (MMP) were employed.

Results: The down-regulation of hTERT expression reduced the invasive activity and MMP expression. This result was re-confirmed in the HSC3 oral squamous carcinoma cell line.

Conclusion: Targeting hTERT may lead to novel therapeutic approaches.

Keywords: Human telomerase reverse transcriptase (hTERT); immortal oral keratinocytes; multi-step process; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / prevention & control*
  • Cell Movement*
  • Cell Proliferation
  • Cell Transformation, Viral / genetics*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Keratinocytes / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / prevention & control*
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus E7 Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / antagonists & inhibitors
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • TERT protein, human
  • Telomerase