The physiological expression of TERT within normal epithelial cells that retain proliferative potential and its presence at the earliest stages of tumorigenesis have implications for the regulation of telomerase expression and for the identification of cells that may be targets for malignant transformation.
These findings overall suggest that TERT expression may be one of the prerequisites for telomerase activation in an early stage of stomach carcinogenesis.
These findings indicate that the up-regulation of hEST2/hTRT gene expression may play a critical role in carcinogenesis of human urinary bladder 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.
Genetic instability, chromosomal instability (telomere reduction), and immortality (activation of telomerase and expression of telomerase reverse transcriptase: TERT) participate in the initial step of stomach carcinogenesis.
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.
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.
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.
Our findings suggest that ISH-based analysis of hTERT gene expression is superior to both TRAP telomerase activity and hTERT mRNA RT-PCR analysis as a means of determining telomerase status during carcinogenesis.
For most tumors it is not clear whether hTERT expression is due to their origin from telomerase positive stem cells or to reactivation of the gene during tumorigenesis.
These results demonstrate a novel pathogenic mechanism whereby mutations in BRCA1, via a novel transcription factor complex containing BRCA1, c-Myc, and Nmi, impair inhibition of c-Myc-induced hTERT promoter activity, which allows sustained activation of telomerase, a key enzyme in carcinogenesis.
These contrasting effects of E2F transcription factors on the hTERT promoter could underlie the paradoxical biological activities of E2F, which can both promote and inhibit cellular proliferation and tumorigenesis.
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.
These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes.
Telomerase reverse transcriptase (hTERT) is the key determinant of telomerase activity and plays a crucial role in cellular immortalization and oncogenesis.
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 findings therefore suggest that ISH-based analysis of hTERT gene expression is superior to TRAP assay as a means of determining telomerase status during carcinogenesis.
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.
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.
To study the changes of human telomerase reverse transcriptase (hTERT) mRNA expression in human hepatocarcinoma cell lines (HepG2) and cholangiocarcinoma cell lines (QBC939) after HBx gene transfection and to illustrate the significance of transcriptional regulation of hTERT gene by HBx gene in the carcinogenesis.