These results indicate that there are at least two steps in the increase of telomerase activity during carcinogenesis in oral squamous cells; a change in distribution of cells expressing these telomerase components and the over-expression of hTERT gene in individual cells.
Thus, this transgenic mouse model provides a suitable in vivo system to analyze the expression of the human TERT gene under physiologic conditions and during tumorigenesis.
To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia.
Human TERT expression was related to the Ki-67 labeling index, indicating that coupling of telomerase activation with cell proliferation was the associated mechanism for tumorigenesis.
Therefore, we propose that loss of CTCF-dependent imprinting of tumor-promoting genes, such as IGF2 and TERT, results from a defective TGF-β pathway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human cancers that are frequently associated with SPTBN1 and SMAD3 mutations.
Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or alternative lengthening of telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis.
Based on these data, we conclude that reactivation of TERT, a direct transcriptional MYC target in tumors, provides a feed-forward mechanism to potentiate MYC-dependent oncogenesis.
It is established that induction of the telomerase reverse transcriptase gene (<i>TERT</i>) coupled with telomerase activation is essential for cancer development/progression and aberrant <i>TERT</i> promoter methylation of specific 5'-C-phosphate-G-3' (CpGs) has been linked to <i>TERT</i> induction in oncogenesis.
Given the significant difference in gene expression profiles between normal and hTERT-immortalized fibroblasts and the close relationship between epiregulin and tumorigenesis, we conclude that hTERT-immortalized cells may not replace their normal counterparts for studies of normal cell biology and that the use of hTERT for expansion of normal human cells for therapeutic purposes must be approached with caution.
Recent studies have suggested polymorphisms in the TERT and CLPTM1L region are associated with carcinogenesis of many distinct cancer types, including gastrointestinal cancers.
Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases.
The human telomerase reverse transcriptase (hTERT) gene encodes the catalytic subunit of telomerase, which mediates pleiotropic effects, including the regulation of senescence and proliferation and plays an important role in carcinogenesis.
These findings provide insight into the role of <i>TERT</i> in ALM tumorigenesis and reveal preliminary evidence that TERT inhibition represents a potential therapeutic strategy in ALM.
The aim of this study was to detect expression of hTERT mRNA, hTERT protein, estrogen receptor (ER) and progesterone receptor (PR) in paraffin-embedded breast tissue samples and to investigate the relationship between hTERT expression and various clinicopathological parameters in breast tumorigenesis.
We found that hTERT, MGMT and DAPK hypermethylation levels were increased during cervical oncogenesis progression. hTERT promoter hypermethylation was able to distinguish normal from cancer (p=0.008), normal from premalignant (p=0.036), as well as premalignant from cervical cancer cases (p=0.003).
Nevertheless, several telomerase catalytic protein signals in the majority of nuclei in precancerous lesions, intraepithelial carcinomas and squamous cell carcinomas, are consistent with telomerase catalytic subunit gene re-expression, an early event in laryngeal carcinogenesis.
Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.
Recently, ASF1a has been shown to be up-regulated in certain human malignancies and required for the expression of telomerase reverse transcriptase (TERT), a factor essential for the immortal phenotype of cancer cells; however, its role in oncogenesis remains poorly defined.
The tumorigenesis, development, dedifferentiation and metastasis of ATC are closely associated with the activation of various tyrosine cascades and inactivation of tumor suppressor genes, including B-Raf proto-oncogene, serine/threonine kinase<sup>V600E</sup>, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α,tumor protein 53 mutations and telomerase reverse transcriptase mutation.
This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.
Analyses of the TERT locus have indicated that non-coding regulatory mutations can be more frequent than previously suspected and play important roles in oncogenesis.