Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis

Jong, Hyun Soon; Park, Young I.; Kim, Sung Hoon; Sohn, Jin Ho; Kang, Sinkyu; Song, Han; Bang, Yung‐Jue; Kim, Noe K.

doi:10.1002/(sici)1097-0142(19990815)86:4<559::aid-cncr3>3.0.co;2-4

Cited by 52 publications

(32 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, we also showed that HSV-1 infection can also upregulate the expression of hTERT in nontumor cells, which may cause further safety concern since upregulation of telomerase has been shown to play a critical role in carcinogenesis. 25,26 Alteration of telomerase activity has been reported in cells infected with HIV and Kaposi's sarcoma-associated herpesvirus. [35][36][37] While HSV-1/2 are not considered carcinogenic, clinical correlation between HSV-2 and human carcinoma of cervix remains to be a debatable issue.…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of human telomerase reverse transcriptase (hTERT) has been shown to play a critical role in carcinogenesis 25,26 and both the hTERT gene and its promoter have higher levels of activity specifically in tumor cells. 27,28 All of these features render the hTERT promoter an attractive target for cancer gene therapy.…”

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

See 1 more Smart Citation

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

View full text Add to dashboard Cite

“…b-actin was amplified to estimate the efficiency of cDNA synthesis as described previously. 13 The PCR products were resolved on 1% agarose gels.…”

Section: Drug Treatment and Rt-pcrmentioning

confidence: 99%

Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma

Kim¹,

Lee²,

Hwang³

et al. 2004

Laboratory Investigation

Self Cite

197

168

View full text Add to dashboard Cite

Accumulating evidence has identified a mechanism potentially responsible for the inactivation of tumor suppressor genes, namely transcriptional silencing by aberrant methylation of CpG islands. A previous study has shown the loss of RUNX3 expression, due to aberrant methylation of its CpG island, in gastric cancer cell lines, suggesting that RUNX3 is a target for epigenetic gene silencing in gastric carcinogenesis. However, there are limited data on the methylation status of RUNX3 in the neoplastic and non-neoplastic tissues in various types of human cancers, including gastric cancer. Here, we report that 60% of gastric cancer cell lines and 64% of primary gastric carcinomas (n ¼ 75) were methylated at the RUNX3 CpG island. RUNX3 methylation was also detected in hepatocellular carcinomas (73%, n ¼ 48), larynx cancers (62%, n ¼ 37), lung cancers (46%, n ¼ 24), breast cancers (25%, n ¼ 25), prostate cancers (23%, n ¼ 44), endometrial cancers (12.5%, n ¼ 24), colon cancers (4.9%, n ¼ 61) and uterine cervical cancers (2.5%, n ¼ 40), showing that RUNX3 methylation is not restricted to gastric cancer. Interestingly, the RUNX3 methylation was especially frequent in tumors from tissues of a foregut derivative, that is, the stomach, liver, larynx and lung. Next, the methylation status of RUNX3 in various nonneoplastic tissues was examined, including the premalignant lesions of gastric carcinomas. The RUNX3 methylation was found in 8.1% of chronic gastritis (n ¼ 99), 28.1% of intestinal metaplasia (n ¼ 32), 27.3% of gastric adenomas (n ¼ 77) and 64% of gastric carcinomas (n ¼ 75), but not in chronic hepatitis B, normal prostate and colon mucosa, even though in cases of chronic hepatitis, the methylation frequency of its neoplastic tissues was very high. In conclusion, RUNX3 methylation is frequently found in human cancers, including gastric cancer, and is mostly cancer specific, with the exception of the stomach, and thus, might be useful as a potential diagnostic biomarker of cancer.

show abstract

“…PCR reactions were performed as follows, 951C for 5 min, and 35 cycles of 951C for 30 s, 551C for 30 s, and 721C for 30 s, followed by incubation at 721C for 10 min. b-actin was amplified, at the same time, to estimate the efficiency of cDNA synthesis as described previously (Jong et al, 1999). PCR products were resolved on 1% agarose gels.…”

Section: Drug Treatment and Rt-pcrmentioning

confidence: 99%

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells

et al. 2003

Self Cite

View full text Add to dashboard Cite

Southern analysis showed that seven of nine human gastric cancer cell lines did not express DLC-1 mRNA, but contained the DLC-1 gene. To identify the mechanism of the loss of DLC-1 mRNA expression in these cell lines, we investigated the methylation status of DLC-1 gene by using methylation-specific PCR (MSP) and Southern blot, and found that five of seven DLC-1 nonexpressing gastric cancer cell lines were methylated in the DLC-1 CpG island. Treatment with 5-aza-2 0 -deoxycytidine (5-Aza-dC) induced DLC-1 mRNA expression in the gastric cancer cell lines that have the methylated alleles. Studies using SNU-601 cell line with methylated DLC-1 alleles revealed that nearly all CpG sites within DLC-1 CpG island were methylated, and that the in vitro methylation of the DLC-1 promoter region is enough to repress DLC-1 mRNA expression, regardless of the presence of transcription factors capable of inducing this gene. In all, 29 of 97 (30%) primary gastric cancers were also shown to be methylated, demonstrating that methylation of the DLC-1 CpG island is not uncommon in gastric cancer. In addition, we demonstrated that DLC-1 mRNA expression was induced, and an increase in the level of acetylated H3 and H4 was detected by the treatment with trichostatin A (TSA) in two DLC-1 nonexpressing cell lines that have the unmethylated alleles. Taken together, the results of our study suggest that the transcriptional silencing of DLC-1, by epigenetic mechanism, may be involved in gastric carcinogenesis.

show abstract

Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis

Cited by 52 publications

References 25 publications

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells

Contact Info

Product

Resources

About