Expression‐patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer

Bettendorf, Olaf; Heine, Bernhard; Kneif, Sören; Eltze, Elke; Semjonow, Axel; Herbst, Hermann; Stein, H.; Böcker, W.; Poremba, Christopher

doi:10.1002/pros.10201

Cited by 24 publications

(19 citation statements)

References 22 publications

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“…Cases with higher hTR expression tended towards earlier recurrence ( Figure 2B), but the difference was not statistically significant according to Kaplan -Meier analysis (log-rank: P ¼ 0.094). In line with previous reports (Bettendorf et al, 2003;Kamradt et al, 2003), no associations with histopathological parameters were observed. Expressions of DKC1 mRNA and hTR were moderately well correlated with each other (Spearman's r: 0.360, P ¼ 0.013).…”

Section: Resultssupporting

confidence: 92%

DKC1 overexpression associated with prostate cancer progression

et al. 2009

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BACKGROUND: Dyskerin encoded by the DKC1 gene is a predominantly nucleolar protein essential for the formation of pseudouridine in RNA and the telomerase RNA subunit hTR. Inherited mutations inactivating dyskerin cause dyskeratosis congenita, a syndrome with progeroid features characterised by skin defects and haematopoiesis failure, as well as cancer susceptibility. In this study, we report DKC1 overexpression in prostate cancers. METHODS: Expression of DKC1 was measured by quantitative RT -PCR in prostate cancer tissues in relation to hTR and the proliferation marker MKI67. Effects of dyskerin downregulation on proliferation, apoptosis and senescence of prostate cancer cell lines were determined. RESULTS: DKC1 was significantly overexpressed in prostate cancers, particularly in high-stage and recurring cases, correlating moderately with hTR and MKI67. Dyskerin downregulation in prostate carcinoma cell lines by siRNA diminished cell proliferation, but elicited neither apoptosis nor senescence. Apoptosis induction by TNF-a or tunicamycin was not enhanced. Long-term downregulation led predominantly to cell shrinking and loss of adhesion. INTERPRETATION: DKC1 upregulation in prostate cancers is common and likely to be necessary for extensive tumour growth. The phenotype of prostate carcinoma cell lines after dyskerin downregulation suggests that its most critical function is sustaining protein biosynthesis. Intriguingly, compromised function and overexpression of dyskerin can both contribute to cancer development.

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Section: Resultssupporting

confidence: 92%

DKC1 overexpression associated with prostate cancer progression

et al. 2009

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“…5b) displayed clear staining of the entire nucleus with simultaneous cytoplasmic staining and non-specific background staining. Our results with the frozen sections were comparable to those published for paraffin sections (18)(19)(20)(21)(22)64,78,79). Like Yan et al (21), we found that this pronounced cytoplasmic staining made evaluation of immunoreactive scores difficult.…”

Section: Correlation Of Htert Score Values and Telomerase Activity Insupporting

confidence: 90%

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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Abstract.In previous studies we demonstrated telomerase activity in frozen tissue from head and neck squamous cell carcinoma (HNSCC) and their tumor-free tumor margins. In the present study frozen sections from the same tissues were examined for in situ presence of hTERT. In preliminary investigations we established that the most suitable method of tissue preparation was fixation in acetone and methanol followed by steaming and visualization by APAAP. Most of the assays involved eleven anti-hTERT antibodies and were supplemented with the inclusion of antibodies Ki-67, antinucleolin and CD45. hTERT expression was investigated in the tissues of 61 patients with HNSCC and 37 patients without tumor. Semi-quantitative immunoreactive scores were correlated with telomerase activity. We examined the prognostic significance of hTERT expression with Kaplan-Meier curves and tested the immunological specificity of the antibodies by immunoabsorption with two hTERT peptides and a nucleolin peptide. Nuclear staining of satisfactory distribution and intensity was achieved in seven anti-hTERT antibodies both in the carcinomas and in the squamous epithelia of the tumor resection margins and in the control tissues. Proof of hTERT did not differ from telomerase activity. The telomerase activity demonstrated in tumor-free resection margins and in control tissues did, however, correlate with lymphocytic-monocytic infiltration (CD45 expression). This telomerase activity might be related to nuclear hTERT expression in the squamous epithelium, given that the hTERT score values in the connective tissue tended to be negative. The prognostic significance of hTERT expression demonstrated on paraffin sections from different tumor localizations was not confirmed for the frozen sections of patients with HNSCC. The hTERT specificity of the monoclonal NCL-L-hTERT, whose use as an antibody against hTERT has been questioned, was reexamined with immunohistochemical methods, but the intensity of its immunoabsorption with the nucleolin peptide did not exceed that observed in the other anti-hTERT antibodies.

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“…The telomerase assay seems, therefore, to be a very useful non-invasive tool to differentiate between Pca and BPH, in contrast with the results of the limited study published by Bettendorf (Bettendorf et al 2003). One of the clinical benefits resulting from this would be to avoid the cost and the complications of prostate biopsy in several subjects without prostate cancer and to refine the clinical indications for biopsy itself.…”

Section: Discussionmentioning

confidence: 67%

“…Moreover other studies demonstrated the presence of telomerase activity in prostatic benign and malignant lesions (Bettendorf et al 2003;Zhang et al 1998). It is possible that TRAP assay is sensitive enough to detect telomerase activity in an early stage of Pca development when any histological alteration is not yet evident, providing a more sensitive means for the detection of infiltrating cancer cells.…”

Section: Discussionmentioning

confidence: 96%

Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia

Vicentini

Gravina

Angelucci

et al. 2004

J Cancer Res Clin Oncol

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Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

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Expression‐patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer

Abstract: No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

Cited by 24 publications

References 22 publications

DKC1 overexpression associated with prostate cancer progression

DKC1 overexpression associated with prostate cancer progression

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia

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