Human telomerase RNA as endogenous control in endometrial tissue

2005 ◽  
Vol 15 (2) ◽  
pp. 343-348
Author(s):  
M. Paul-Samojedny ◽  
A. Witek ◽  
A. Samojedny ◽  
A. Witkowska ◽  
T. Wilczok

Telomerase is a reverse transcriptase that adds repetitive telomere sequences to the end of chromosomes, which is thought to be essential for cellular immortality and oncogenesis. The enzyme 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. But many studies have revealed that hTR and TP1 are expressed constitutively. This resuts suggest that the hTR and TP1 subunits may be potentially good markers of endogenous RNA control. Endometrial dating was determined from the pathomorphology of the endometrium and classified into normal proliferative endometrium, endometrial hyperplasia (simple, complex, and atypical), and endometrial adenocarcinoma. The analysis of the expression of the hTERT, TP1, and hTR telomerase subunits was performed by a quantitative polymerase chain reaction method, based on fluorescent TaqMan methodology (ABI Prism 7 700 Sequence Detection System) capable of measuring fluorescence in real time. The aim of the study was an analysis of the expression profiles of genes encoding hTR and TP1 telomerase subunits in normal endometrium, endometrial hyperplasia, and adenocarcinoma forthe estimation of the possibility of once application in endogenous RNA control of gene analysis in the endometrium. The nonparametric Mann–Whitney U test and analysis of variance Friedman test were used to evaluate the variation in telomerase subunit mRNA level between normal endometrium, and endometrial hyperplasia and adenocarcinoma. The results confirm the hTR subunit expression as a good marker of endogenous control in quantitative analysis of gene transcription in endometrial tissue. TP1 subunit transcriptions have not been detected constitutively in our study.

2005 ◽  
Vol 15 (2) ◽  
pp. 343-348 ◽  
Author(s):  
M. Paul-Samojedny ◽  
A. Witek ◽  
A. Samojedny ◽  
A. Witkowska ◽  
T. Wilczok

2000 ◽  
Vol 275 (29) ◽  
pp. 22568-22573 ◽  
Author(s):  
Kenkichi Masutomi ◽  
Shuichi Kaneko ◽  
Naoyuki Hayashi ◽  
Tatsuya Yamashita ◽  
Yukihiro Shirota ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259330
Author(s):  
Nien-Tzu Liu ◽  
Cherng-Lih Perng ◽  
Yu-Ching Chou ◽  
Pi-Shao Ko ◽  
Yi-Jia Lin ◽  
...  

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.


2021 ◽  
Vol 6 (5) ◽  
pp. 89-94
Author(s):  
M. S. Lyndin ◽  
◽  
O. I. Kravtsova ◽  
V. V. Sikora ◽  
N. I. Hyriavenko ◽  
...  

Endometrioid endometrial adenocarcinomas are the most common histological variant of malignant tumors in the uterine cavity. In turn, the features of expression by neoplastic cells of intercellular adhesion molecules are a reliable prognostic factor in the progression of malignant tumors. One of the important indicators of cancer progression is E-cadherin, which determines the strength of intercellular adhesion and the ability of cells to spread. Among other adhesion molecules, considerable attention has recently been paid to the molecules of cell adhesion of carcino-embryonic antigen 1 (MCA-REA1). Therefore, the purpose of the study was to study the expression of E-cadherin and MCA-REA1 in normal endometrium and endometrioid adenocarcinomas. Materials and methods. To achieve this purpose, we performed tissue studies of 10 samples of normal endometrium and 30 samples of endometrioid endometrial adenocarcinoma (8380/3). Morphological features of neoplastic tissue were studied by hematoxylin and eosin staining. Visualization of E-cadherin and MCA-REA1 receptors was determined using the appropriate antibodies and the UltraVision Quanto Detection System HRP DAB Chromogen (Thermo scientific, USA) in similar areas of the tumor on serial sections. Results and discussion. It has been shown that endometrial tissue demonstrates different expression of MCA-REA1 and E-cadherin receptors in the normal state and in endometrioid adenocarcinomas. This indicates the absence of any functional correlation between them. Expression of MCA-REA1 was detected on the apical surface of the luminal and glandular columnar epithelium. In contrast, the endometrioid endometrial carcinoma tissues showed the pronounced heterogeneous location of MCA-REA1 in tumor cells. Moreover, due to the tumor dedifferentiation, these proteins disappear from the cell surface. On the other hand, E-cadherin is normally localized in intercellular contacts and epithelial-mesenchymal junctions. During carcinoma dedifferentiation, the intensity of E-cadherin expression decreased, which was accompanied by an increase in nuclear polymorphism of cancer cells and focal separation of cells from the total tumor mass. Conclusion. The variability of the expression patterns of MCA-REA1 and E-cadherin in the dedifferentiation of endometrioid adenocarcinoma may be an indicator of neoplastic transformation and progression of the malignant process


2002 ◽  
Vol 22 (4) ◽  
pp. 1253-1265 ◽  
Author(s):  
Tara J. Moriarty ◽  
Sylvain Huard ◽  
Sophie Dupuis ◽  
Chantal Autexier

ABSTRACT Functional human telomerase complexes are minimally composed of the human telomerase RNA (hTR) and a catalytic subunit (human telomerase reverse transcriptase [hTERT]) containing reverse transcriptase (RT)-like motifs. The N terminus of TERT proteins is unique to the telomerase family and has been implicated in catalysis, telomerase RNA binding, and telomerase multimerization, and conserved motifs have been identified by alignment of TERT sequences from multiple organisms. We studied hTERT proteins containing N-terminal deletions or substitutions to identify and characterize hTERT domains mediating telomerase catalytic activity, hTR binding, and hTERT multimerization. Using multiple sequence alignment, we identified two vertebrate-conserved TERT N-terminal regions containing vertebrate-specific residues that were required for human telomerase activity. We identified two RNA interaction domains, RID1 and RID2, the latter containing a vertebrate-specific RNA binding motif. Mutations in RID2 reduced the association of hTR with hTERT by 50 to 70%. Inactive mutants defective in RID2-mediated hTR binding failed to complement an inactive hTERT mutant containing an RT motif substitution to reconstitute activity. Our results suggest that functional hTERT complementation requires intact RID2 and RT domains on the same hTERT molecule and is dependent on hTR and the N terminus.


2003 ◽  
Vol 16 (7) ◽  
pp. 700-707 ◽  
Author(s):  
Jinyoung Yoo ◽  
Sonya Y Park ◽  
Seok Jin Kang ◽  
Byung Kee Kim ◽  
Sang In Shim ◽  
...  

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