Human telomerase reverse transcriptase is a promising target for cancer inhibition in squamous cell carcinomas.
نویسندگان
چکیده
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.
منابع مشابه
TELOMERASEACTIVITYIN IRANIAN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Telomerase activation is one of the main pathways to immortalize cancer cells. In many kinds of cancer cells, this special reverse transcriptase stabilizes and elongates telomeres and prevents telomere erosion that naturally occurs in every cell division. Esophageal cancer is the fifth most frequent cause of cancer death worldwide, and is highly associated with alcohol, smoking, cultural ha...
متن کاملExpression Pattern of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase (hTERT) in Cancer Cell Lines Was not Associated with the Origin of the Cells
Telomerase and systems controlling their activity have been of great attention. There are controversies regarding the role of the alternative splicing forms of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Therefore, the correlation between telomerase enzyme activity, the abundance of alternatively spliced variants of hTERT and doubling time of a seri...
متن کاملTelomerase inhibition enhances the response to anticancer drug treatment in human breast cancer cells.
Breast cancer is the most common malignancy among women. Current therapies for breast tumors are based on the use of chemotherapeutic drugs that are quite toxic for the patients and often result in resistance. Telomerase is up-regulated in 95% of breast carcinomas but not in adjacent normal tissues. Therefore, it represents a very promising target for anticancer therapies. Unfortunately, the an...
متن کاملInhibition of telomerase activity in human cancer cells by RNA interference.
Telomerase is an attractive molecular target toward which to direct cancer therapeutic agents because telomerase activity is present in most malignant cells but undetectable in most normal somatic cells. Short duplex RNA (short-interfering RNA or siRNA) has recently been shown to be an effective method for inhibiting the expression of a given gene in human cells. Accordingly, we evaluated the a...
متن کاملBlockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ ERK signaling pathways
Head and Neck squamous cell carcinomas (HNSCC), characterized by the high frequency of local recurrence and distant metastases, is mostly related to highly malignant and resistant to apoptosis, resulting in significant insensitivity to chemotherapy. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, was implicated in the telomerase-mediated cellular transformation,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Anticancer research
دوره 34 11 شماره
صفحات -
تاریخ انتشار 2014