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

Young-Jin Park; Eun-Kyoung Kim; Sook Moon; Doo-Pyo Hong; Jung Yoon Bae; Jin Kim

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

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

Authors

Young-Jin Park¹, Eun-Kyoung Kim¹, Sook Moon¹, Doo-Pyo Hong¹, Jung Yoon Bae¹, Jin Kim²

Affiliations

¹ Department of Oral Pathology, Oral Cancer Research Institute and Brain Korea PLUS 21 Project, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
² Department of Oral Pathology, Oral Cancer Research Institute and Brain Korea PLUS 21 Project, College of Dentistry, Yonsei University, Seoul, Republic of Korea [email protected].

PMID: 25368238

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