The detection and quantitative analysis of telomerase activity and TERT expression is helpful for distinguishing malignant from normal endometrium when the patient is postmenopausal, even if the tumor is very small or of low malignancy.
In conclusion, the simple and rapid method of hEST2 RT-PCR serves to support the cytologic diagnosis of malignancy, but false-positive PCR results resulting from activated lymphocytes and proliferating mesothelial cells must be considered.
The tight specificity of expression imparted by the hTERT promoter will assist the development of novel approaches to the treatment of a broad array of cancer types.
Regarding all carcinomas, no statistically significant correlation was observed between hTR-expression and tumor stage, lymph node or distant metastasis. hTERT-expression was associated with malignancy and tumor stage.
Telomerase activation, a cardinal requirement for immortalization, is a crucial step in the development of malignancy and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene.
Human cancer cell lines were transfected with 21 nt double-stranded RNA homologous to either the catalytic subunit of telomerase (human telomerase reverse transcriptase) or to its template RNA [human telomerase RNA(hTR)].
While the wild-type Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect only in cancer cells.
To investigate the possibility of utilizing the hTERT promoter and the SV40 enhancer in targeted cancer gene therapy, we constructed an adenovirus vector expressing HSV-TK controlled by the hTERT promoter and the SV40 enhancer for the induction of specific telomerase positive cancer cell death.
Genes in the Ad E4 transcription unit are essential for Ad replication; therefore, VRX-011 will grow efficiently only in cells in which the hTERT promoter is active, that is, in a wide range of cancer and immortalized cells but not in most somatic cells.
A number of cancer-specific promoters have been reported, such as those of probasin, human telomerase reverse transcriptase, survivin, ceruloplasmin, HER-2, osteocalcin, and carcinoembryonic antigen.
Telomerase and its catalytic subunit, telomerase reverse transcriptase (hTERT), are specifically expressed in cancers, making them candidate markers for the early detection of cancer.
These results, particularly the lack of problematic levels of S-phase-specific activation of hTERT promoters in normal cells, have promising implications for hTERT promoter-based targeted gene therapy of cancer.
In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice.
Here, telomerase catalytic subunit (hTERT) activity and heat shock protein 90 expression could serve both as molecular markers allowing an earlier diagnosis of malignancy and as therapeutic targets.