Overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in head and neck squamous cell carcinomas

Nguyen, Dan C.; Parsa, Behdad; Close, Abby; Magnusson, Bengt; Crowe, David L.; Sinha, Uttam K.

doi:10.3892/ijo.22.6.1285

Cited by 23 publications

(29 citation statements)

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“…The patterns of hTERT expression in these frozen sections did not vary essentially from the picture presented on the paraffin sections from HNSCC already examined (47)(48)(49)(50)(51). With an antibody not described in more detail, Nguyen et al (47) demonstrated hTERT in all carcinomas examined and, albeit significantly less, in dysplastic squamous epithelia.…”

Section: Discussionmentioning

confidence: 55%

“…With an antibody not described in more detail, Nguyen et al (47) demonstrated hTERT in all carcinomas examined and, albeit significantly less, in dysplastic squamous epithelia. The authors (47) suppose a correlation between hTERT expression and tumor stage.…”

Section: Discussionmentioning

confidence: 97%

“…None of the few immunohistochemical studies dealing with hTERT on squamous cell carcinomas in the head and neck has correlated its results to telomerase activity (47)(48)(49)(50)(51). Gonzalez-Quevedo et al (52), who demonstrated hTERT in the RT-PCR in various tumors, pointed to a direct correlation between telomerase activity (determined in TRAP-ELISA) and hTERT.…”

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 97%

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 99%

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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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“…22 Our data of overexpressed EGFR in squamous cell carcinoma of the tonsil are also consistent with other reports. 1,2 In addition, we found that high-grade dysplasia was characterized statistically by overexpression of EGFR at the top 1/3 of the squamous epithelium, which may be used as a morphoproteomic marker for confirming the highgrade dysplasia. Moreover, we found that p-Akt was highly expressed in squamous cell carcinoma of the tonsil, confirming one study reported in 2002 23 and also in high-grade dysplasia.…”

Section: Discussionmentioning

confidence: 91%

“…1 Immunohistochemical demonstration of EGFR overexpression in head and neck squamous cell carcinoma has been correlated with a high mitotic index and advanced (stage III and IV) tumors. 2 In a phase II clinical trial in refractory head and neck squamous cell carcinoma, ZD1839 (Iressa), targeted at EGFR, had single-agent activity with a 10.6% response rate and a disease control rate of 53% and was well tolerated. 3 The downstream signals of EGFR such as ras protein (activated through farnesyl transferase), Akt and nuclear factor-kappa B (NF-kB) all may be related to the tumorigenesis of head and neck squamous cell carcinoma.…”

mentioning

confidence: 99%

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis

et al. 2005

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Downregulation of c-myc protein by siRNA-mediated silencing of DNA-PKcs in HeLa cells

Jianli

et al. 2005

Int. J. Cancer

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DNA-dependent protein kinase (DNA-PK) has been intensively investigated for its roles in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break repair and maintenance of genomic stability. Its catalytic subunit, DNA-PKcs, a serine/threonine protein kinase, has recently been reported to be overexpressed in various human cancers, but its significance is unclear. In our study, we synthesized 3 small interfering RNA (siRNA) oligonucleotides, which separately target the translation initiation region, catalytic motif and a sequence between the scidmutation region and the FATC motif of DNA-PKcs; 3 stable cell lines were generated from HeLa cells transfected with these siRNA constructs, respectively. All 3 siRNAs resulted in remarkable depression on DNA-PKcs expression in HeLa cells, and led to an increased sensitivity to 2 or 4 Gy of g-ray as well as 5 or 10 J/ m 2 of ultraviolet (UV) irradiation. The siRNA targeting the catalytic motif of DNA-PKcs exhibited the greatest efficiency of radiosensitization. We demonstrated that c-myc protein level was suppressed more than 80% by siRNA-mediated silencing of DNAPKcs. Using an E-box enhancer (c-myc binding element) driving a secreted alkaline phosphatase (SEAP) reporter strategy, we further found that the transcriptional activity of c-myc was extremely suppressed by silencing DNA-PKcs. The highest suppression effect on c-myc expression was observed in the cells transfected with the siRNA targeting the catalytic motif of DNA-PKcs. Moreover, a similar suppression on c-myc expression and activity was also detected in HeLa cells treated with wortmannin, a phosphatidylinositol (PI)-3 kinase inhibitor. However, silencing DNA-PKcs did not change the level of c-myc mRNA. We have further identified the interaction between DNA-PKcs and c-myc protein. Together, our results imply that DNA-PKcs activity is necessary or contributory to the expression of c-myc protein. Targeting DNA-PKcs is an attractive anticancer strategy, which can achieve through at least two mechanistic pathways: (i) sensitizing cancer cells to radiotherapy or chemotherapy of DNA-damaging agents and (ii) downregulation of c-myc protein. ' 2005 Wiley-Liss, Inc.

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Overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in head and neck squamous cell carcinomas

Cited by 23 publications

References 0 publications

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

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

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis

Downregulation of c-myc protein by siRNA-mediated silencing of DNA-PKcs in HeLa cells

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