An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection

Lin, Tzu-Chen; Lee, Huei; Chen, Ruei-A; Ho, Ming-Lin; Lin, Chujun; Chen, Yahui; Tsai, Yi Yu; Chou, Ming-Chih; Cheng, Ya‐Wen

doi:10.1016/j.canlet.2004.12.031

Cited by 43 publications

(35 citation statements)

References 28 publications

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“…Studies using SCC samples shed light on the role of high-risk HPV infection in epigenetic regulation (43). For example, it was suggested that HPV-16 induces the methylation of p16 CDKN2A (44); however, as oncogenic HPV neutralises phosphorylated Rb (PRb)-mediated control of the cell cycle, there would be no advantage for the HPV-infected host cell to block the same signalling pathway at another checkpoint by downregulating p16 CDKN2A (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

et al. 2012

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Abstract.Recently, high-risk human papillomavirus (HPV) has emerged as a possible agent associated with head and neck squamous cell carcinoma (HNSCC) in younger patients. Therefore, the purpose of the present study was to assess the effect of age on the distribution of HPV-16/18 in HNSCC, together with the impact of the virus on patient prognosis. A longitudinal prospective study was used adjusted for age, gender, TNM staging, smoking status and alcohol consumption. HPV was detected by PCR with consensus primers. Results showed there was no difference in the frequency of HPV-16/18 positivity when younger patients were compared to the older patients. No association was found among highrisk HPV positivity, gender, smoking habit and anatomical site. High-risk HPV was associated with advanced TNM in bivariate analyses; however, it did not impact on survival. Only TNM staging was associated with risk of mortality. Our study supports the theory that age does not affect the presence of HPV-16/18 in HNSCC and has no impact on patient prognosis. The incidence of HNSCC among patients under the age of 45 years is reportedly on the increase worldwide. The factors associated with HNSCC in younger adults are not well established. Findings of this study indicate that HPV-16/18 may not play a role in HNSCC patients under the age of 45 years.

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Section: Discussionmentioning

confidence: 99%

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

et al. 2012

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“…12,14 In our study, we demonstrated a strong correlation between the elevated expression of DNMT3b mRNA and hypermethylation of p16, and this result was consistent with the previous report in lung cancer. 16 If two or more methylated genes were considered, the increased expression of DNMT3b mRNA was correlated with hypermethylation of multiple genes. Our data suggest that DNMT3b upregulation may mainly contribute to aberrant methylation pattern in ESCC development.…”

Section: Discussionmentioning

confidence: 99%

“…All the slides were inspected under double blindness and independently by two experienced pathologists. The positive cells were counted and classified into five grades according to previously described criteria: 16 score 0, no positive cell staining; score +, <10%; score ++, from 11-50%; score +++, from 51-70%; score ++++, >70% positive cells. In this study, scores +, intriguing because currently available serum biomarkers such as CEA and CA199 were less informative for the early detection of ESCC.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of multiple tumor-related genes associated with DMNT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma

Li¹,

Wang²,

Niu³

et al. 2011

Epigenetics

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“…Moreover, hypermethylation of various tumor suppressor genes causes their transcriptional silencing and removes a barrier of normal proliferation, which may result in malignant transformation. Most interestingly, overexpression of DNMT1 and DNMT3B has been found to be common in human tumors (14)(15)(16)(17), and this overexpression could also be associated with HPV infections (18)(19)(20) residues. These modifications are mediated by proline hydroxylases (PHDs), whose activity is regulated by O 2 availability (22).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

Łuczak

Roszak²,

Pawlik³

et al. 2011

Int J Oncol

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Abstract. The development of cervical cancer requires genetic and epigenetic factors which result in the persistence of a malignant phenotype. Cervical cancer exhibits also some unique differences from other solid tumors. Normal cervical stratified epithelia have characteristics of hypoxic tissue with over-expression of HIF-1 (hypoxia-inducible factor-1) transcription factor, which targets the transcription of over 70 genes involved in many aspects of cancer biology. One of the genes, which could be induced by HIF-1 is chemokine (C-X-C motif) receptor 4 (CXCR4). CXCR4 could also be epigenetically regulated by methylation of CpG dinucleotides located in the promoter region. Here, we examined the CXCR4, DNMT3A, DNMT3B and DNMT1 transcript levels in cancer tissue (n=30) and non-cancer, normal uterine cervical tissue (n=30) from a Polish cohort. We also compared the methylation status of CXCR4 promoter region in cancer and normal tissue samples. Our result showed significantly higher levels of CXCR4, DNMT3A, DNMT3B and DNMT1 transcript (p=0.0058, 0.0163, 0.0003 and <0.0001, respectively) levels in cancer tissue as compared to normal samples. We did not observe DNA methylation in the CXCR4 promoter region in either control or cancer tissue samples. CXCR4 has a functional hypoxia response element (HRE) in the promoter region, located -1.3 kb from the transcription start site. Our work shows for the first time that HIF-1A could promote the induction of CXCR4 gene expression (Spearman's correlation coefficient = 0.515, p=0.003) in patients with primary advanced

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An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection

Cited by 43 publications

References 28 publications

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

Hypermethylation of multiple tumor-related genes associated with DMNT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

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