Comparison of telomerase activity in normal chorionic villi to trophoblastic diseases.

Nishi, Hirotaka; Yahata, Naoyuki; Ohyashiki, Kazuma; Isaka, Keiichi; Shiraishi, Kei; Ohyashiki, J H; Toyama, Keisuke; Takayama, M.

doi:10.3892/ijo.12.1.81

Cited by 22 publications

(26 citation statements)

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“…The finding of increased HIF-1␣ protein expression in the first trimester is consistent with the low intervillous blood flow and physiological hypoxia that have been reported during the early stages of placental development (32). In the present study we also show that the HIF-1␣ expression correlates with hTERT expression (and telomerase activity), which decreases with increased gestational age (19,29). For the first time we show that the transcription factor HIF-1 induces hTERT expression.…”

Section: Discussionmentioning

confidence: 48%

“…We examined hTERT mRNA expression in 22 normal chorionic villi obtained from 6 to 10 weeks of gestation and 15 placentas from 12 to 41 weeks by RT-PCR by using previously reported methods (7,28,29). Although 20 of the normal chorionic villi from the 6-to 10-week gestational period had hTERT expression, placenta tissues from the 12-to 41-week period were negative except for four cases (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It was previously reported that trophoblasts from trophoblastic diseases and normal chorionic villi in early pregnancy expressed relatively high levels of telomerase activity and that the levels of telomerase activity in normal human villi tended to decrease depending on gestational age (19,29). The expression of the human telomerase catalytic subunit (hTERT) correlates with telomerase activity (24,26,41).…”

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confidence: 99%

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Hypoxia-Inducible Factor 1 Mediates Upregulation of Telomerase (hTERT)

Nishi

Nakada

Kyo

et al. 2004

Molecular and Cellular Biology

189

136

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Hypoxia occurs during the development of the placenta in the first trimester and correlates with both trophoblast differentiation and the induction of telomerase activity through hTERT expression. We sought to determine the mechanism of regulation of hTERT expression during hypoxia. We show that hypoxia-inducible factor 1␣ (HIF-1␣) and hTERT expression in the human placenta decrease with gestational age and that these are overexpressed in preeclamptic placenta, a major complication of pregnancy. Hypoxia not only transactivates the hTERT promoter activity but also enhances endogenous hTERT expression. The hTERT promoter region between ؊165 and ؉51 contains two HIF-1 consensus motifs, and in vitro reporter assays show that these are essential for hTERT transactivation by HIF-1. Introduction of an antisense oligonucleotide for HIF-1 diminishes hTERT expression during hypoxia, indicating that upregulation of hTERT by hypoxia is directly mediated through HIF-1. Our results provide persuasive evidence that the regulation of hTERT promoter activity by HIF-1 represents a mechanism for trophoblast growth during hypoxia and suggests that this may be a generalized response to hypoxia in various human disorders including resistance to cancer therapeutics by upregulating telomerase.

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Section: Discussionmentioning

confidence: 48%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Hypoxia-Inducible Factor 1 Mediates Upregulation of Telomerase (hTERT)

Nishi

Nakada

Kyo

et al. 2004

Molecular and Cellular Biology

189

136

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“…Telomerase activity was reported to be between 12.5% and 86.7% in complete moles and 100% in choriocarcinomas (30)(31)(32). In this study, hTERT activity was found to be negative in the single gestational trophoblastic tissue sample; we believe that this was related to the low proliferation rate of gestational trophoblastic diseases and may also indicate a favourable prognosis for the disease.…”

Section: Discussionmentioning

confidence: 65%

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

Gül¹,

Dündar²,

Bodur³

et al. 2013

Balkan Med J

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Background: Telomeres are essential for the function and stability of eukaryotic chromosomes. Telomerase consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. Telomerase activity is a useful cancer-cell detecting marker in some types of cancers.Aims: The aim of this study was to assess of telomerase hTERT mRNA in gynaecological tumors for diagnosis of malignancy.Study Design: Cross-sectional study.Methods: A total of 55 gynaecologic tumor samples (35 ovarian, 13 endometrial, 6 cervical and 1 placental site trophoblastic tumor tissue) were obtained at the time of surgery. Quantification of hTERT mRNA was performed in a real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the LightCycler TeloTAGGG hTERT Quantification Kit.Results: It was histopathologically detected that 18 of the tissue samples were malignant and 37 of the samples were benign. 16 of the malignant tissue samples (88.9%) and 3 (8.1%) (endometrial tissue in proliferative phase, mucinous cyst adenoma and endometriosis) of the benign tissue samples were found to be hTERT positive. With the presence of these data, sensitivity and specificity of hTERT for the diagnosis of malignancy were calculated to be 88.9% and 91.9%, respectively. Conclusion:It was suggested that the measurement of telomerase activity in gynaecologic tumors, except for endometrial tissue in the reproductive phase, is a valuable method for pathological investigation.

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“…the proliferative compartment, and was switched o with dierentiation (HaÈ rle-Bachor and Boukamp 1996). In endometrium, enzyme activity was highest in the late proliferative phase of the menstural cycle (Kyo et al 1997;Saito et al 1997) and in normal chorionic villi samples the level depended on the gestational age (Nishi et al 1998). For normal gastrointestinal mucosa, on the other hand, contradictory results have been reported.…”

Section: Introductionmentioning

confidence: 95%

Telomerase is active in normal gastrointestinal mucosa and not up-regulated in precancerous lesions

Bachor

Boukamp

1999

Journal of Cancer Research and Clinical Oncology

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Telomerase is a ribonucleoprotein complex which, by de novo synthesized telomeric TTAGGG repeats, prevents telomere erosion. While telomerase is active in most cancers, conflicting results exist for normal tissues and premalignant lesions. To establish the telomerase status of normal gastrointestinal mucosa and to elucidate whether telomerase up-regulation is an early or late event in carcinogenesis, we determined the telomerase activity of 88 biopsies of normal mucosa from esophagus, stomach, and intestine and compared it with that of 21 samples of premalignant lesions and 6 adenocarcinomas using the telomere-repeat amplification protocol assay. Telomerase was found in all normal tissues, revealing most activity in esophagus (11 samples), followed by intestine (45 samples), and stomach (32 samples). In 53% of the stomach samples, enzyme activity could only be demonstrated when telomerase inhibitors were eliminated by a modified telomerase assay. In the 21 precancerous lesions (5 Barrett's esophagus, 3 stomach intestinal metaplasias, and 13 colorectal adenomas of type I/II dysplasia) a similar or even reduced telomerase activity was seen, while the adenocarcinomas showed high activity. These data demonstrate that telomerase activity is expressed in all epithelia along the gastrointestinal tract, thus confirming our previous hypothesis that telomerase is constitutively expressed in permanently renewing epithelia. Furthermore, activity was not increased in preneoplastic lesions, suggesting that telomerase up-regulation is a late event during carcinogenesis of the esophagus, stomach, and intestine.

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Comparison of telomerase activity in normal chorionic villi to trophoblastic diseases.

Cited by 22 publications

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Hypoxia-Inducible Factor 1 Mediates Upregulation of Telomerase (hTERT)

Hypoxia-Inducible Factor 1 Mediates Upregulation of Telomerase (hTERT)

The Status of Telomerase Enzyme Activity in Benign and Malignant Gynaecologic Pathologies

Telomerase is active in normal gastrointestinal mucosa and not up-regulated in precancerous lesions

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