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Methylation-related silencing of p14ARF gene correlates with telomerase activity and mRNA expression of human telomerase reverse transcriptase in hepatocellular carcinoma.
J Surg Oncol. 2008 Nov 01; 98(6):462-8.JS

Abstract

BACKGROUND AND OBJECTIVES

The p14(ARF) gene encodes a critical negative regulator of cell cycle progression. And upregulation of telomerase activity has been considered a critical step to tumors. We investigated promoter methylation of p14(ARF) and expression as well as their effect on hTERT expression and telomerase activity in HCC.

METHODS

We studied p14(ARF) methylation and mRNA in 30 hepatocellular carcinomas and corresponding non-tumor liver tissues using methylation-specific PCR. Reverse transcription-PCR was performed for expression of p14(ARF) and hTERT. Telomerase activity was performed by TRAP assay.

RESULTS

p14(ARF) hypermethylation was detected in 16 (53.3%) of HCC and 10 (33.3%) of non-tumor tissues, and 12 of 16 with methylation were tumor tissues around large size (> or =5 cm). p14(ARF) mRNA was observed in 25%, 80.0%, or 50.0% of tumors with hypermethylated, partially methylated or unmethylated p14(ARF) promoter, respectively. Among the 16 tumors with p14(ARF) hypermethylation, all 12 tumors lacking p14(ARF) mRNA were positive for hTERT expression, while only one of 4 tumors expressing p14(ARF) mRNA was positive for hTERT expression.

CONCLUSIONS

p14(ARF) hypermethylation may contribute to silencing of p14(ARF) mRNA expression in HCC. Telomerase activity is association with inactivation of the p14(ARF)-p53 pathway induced by methylation in HCC.

Authors+Show Affiliations

Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18683194

Citation

Zhang, Changsong, et al. "Methylation-related Silencing of p14ARF Gene Correlates With Telomerase Activity and mRNA Expression of Human Telomerase Reverse Transcriptase in Hepatocellular Carcinoma." Journal of Surgical Oncology, vol. 98, no. 6, 2008, pp. 462-8.
Zhang C, Guo X, Zhang L, et al. Methylation-related silencing of p14ARF gene correlates with telomerase activity and mRNA expression of human telomerase reverse transcriptase in hepatocellular carcinoma. J Surg Oncol. 2008;98(6):462-8.
Zhang, C., Guo, X., Zhang, L., Lu, Z., Ma, N., Cheng, Y., Shen, F., Zhang, B., Wu, M., & Wei, L. (2008). Methylation-related silencing of p14ARF gene correlates with telomerase activity and mRNA expression of human telomerase reverse transcriptase in hepatocellular carcinoma. Journal of Surgical Oncology, 98(6), 462-8. https://doi.org/10.1002/jso.21131
Zhang C, et al. Methylation-related Silencing of p14ARF Gene Correlates With Telomerase Activity and mRNA Expression of Human Telomerase Reverse Transcriptase in Hepatocellular Carcinoma. J Surg Oncol. 2008 Nov 1;98(6):462-8. PubMed PMID: 18683194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylation-related silencing of p14ARF gene correlates with telomerase activity and mRNA expression of human telomerase reverse transcriptase in hepatocellular carcinoma. AU - Zhang,Changsong, AU - Guo,Xianling, AU - Zhang,Li, AU - Lu,Zhenghua, AU - Ma,Nannan, AU - Cheng,Yue, AU - Shen,Feng, AU - Zhang,Baihe, AU - Wu,Mengchao, AU - Wei,Lixin, PY - 2008/8/7/pubmed PY - 2008/11/19/medline PY - 2008/8/7/entrez SP - 462 EP - 8 JF - Journal of surgical oncology JO - J Surg Oncol VL - 98 IS - 6 N2 - BACKGROUND AND OBJECTIVES: The p14(ARF) gene encodes a critical negative regulator of cell cycle progression. And upregulation of telomerase activity has been considered a critical step to tumors. We investigated promoter methylation of p14(ARF) and expression as well as their effect on hTERT expression and telomerase activity in HCC. METHODS: We studied p14(ARF) methylation and mRNA in 30 hepatocellular carcinomas and corresponding non-tumor liver tissues using methylation-specific PCR. Reverse transcription-PCR was performed for expression of p14(ARF) and hTERT. Telomerase activity was performed by TRAP assay. RESULTS: p14(ARF) hypermethylation was detected in 16 (53.3%) of HCC and 10 (33.3%) of non-tumor tissues, and 12 of 16 with methylation were tumor tissues around large size (> or =5 cm). p14(ARF) mRNA was observed in 25%, 80.0%, or 50.0% of tumors with hypermethylated, partially methylated or unmethylated p14(ARF) promoter, respectively. Among the 16 tumors with p14(ARF) hypermethylation, all 12 tumors lacking p14(ARF) mRNA were positive for hTERT expression, while only one of 4 tumors expressing p14(ARF) mRNA was positive for hTERT expression. CONCLUSIONS: p14(ARF) hypermethylation may contribute to silencing of p14(ARF) mRNA expression in HCC. Telomerase activity is association with inactivation of the p14(ARF)-p53 pathway induced by methylation in HCC. SN - 1096-9098 UR - https://www.unboundmedicine.com/medline/citation/18683194/Methylation_related_silencing_of_p14ARF_gene_correlates_with_telomerase_activity_and_mRNA_expression_of_human_telomerase_reverse_transcriptase_in_hepatocellular_carcinoma_ L2 - https://doi.org/10.1002/jso.21131 DB - PRIME DP - Unbound Medicine ER -