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METH-2 silencing and promoter hypermethylation in NSCLC.

Dunn JR, Panutsopulos D, Shaw MW, Heighway J, Dormer R, Salmo EN, Watson SG, Field JK, Liloglou T - Br. J. Cancer (2004)

Bottom Line: This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed.Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs.No homozygous deletions of METH-2 were found in lung cancer cell lines.

View Article: PubMed Central - PubMed

Affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK.

ABSTRACT
The antiangiogenic factor METH-2 (ADAMTS-8) was identified in a previous dual-channel cDNA microarray analysis to be at least two-fold under-represented in 85% (28 out of 33) of primary non-small-cell lung carcinomas (NSCLCs). This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed. Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs. DNA methylation analysis of the proximal promoter region of this gene revealed abnormal hypermethylation in 67% of the adenocarcinomas and 50% of squamous cell carcinomas, indicating that epigenetic mechanisms are involved in silencing this gene in NSCLC. No homozygous deletions of METH-2 were found in lung cancer cell lines. Allelic imbalance in METH-2 was assessed by an intronic single nucleotide polymorphism (SNP) assay and observed in 44% of informative primary samples. In conclusion, the downregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease.

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Related in: MedlinePlus

Relative expression levels of METH-2 in paired normal and tumour lung tissues. Patient numbers are shown. The heavier band represents the control gene (O28) and the lower band represents METH-2. A remarkable reduction of METH-2 transcript is observed in all tumour samples. N: normal; T: tumour.
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fig1: Relative expression levels of METH-2 in paired normal and tumour lung tissues. Patient numbers are shown. The heavier band represents the control gene (O28) and the lower band represents METH-2. A remarkable reduction of METH-2 transcript is observed in all tumour samples. N: normal; T: tumour.

Mentions: Comparative multiplex RT–PCR (cmRT–PCR) analysis of METH-2 in 23 paired normal and lung cancer tissue cDNAs demonstrated a dramatic reduction of METH-2 transcript in 23 out of 23 (100%) lung tumour samples (Figure 1Figure 1


METH-2 silencing and promoter hypermethylation in NSCLC.

Dunn JR, Panutsopulos D, Shaw MW, Heighway J, Dormer R, Salmo EN, Watson SG, Field JK, Liloglou T - Br. J. Cancer (2004)

Relative expression levels of METH-2 in paired normal and tumour lung tissues. Patient numbers are shown. The heavier band represents the control gene (O28) and the lower band represents METH-2. A remarkable reduction of METH-2 transcript is observed in all tumour samples. N: normal; T: tumour.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747718&req=5

fig1: Relative expression levels of METH-2 in paired normal and tumour lung tissues. Patient numbers are shown. The heavier band represents the control gene (O28) and the lower band represents METH-2. A remarkable reduction of METH-2 transcript is observed in all tumour samples. N: normal; T: tumour.
Mentions: Comparative multiplex RT–PCR (cmRT–PCR) analysis of METH-2 in 23 paired normal and lung cancer tissue cDNAs demonstrated a dramatic reduction of METH-2 transcript in 23 out of 23 (100%) lung tumour samples (Figure 1Figure 1

Bottom Line: This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed.Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs.No homozygous deletions of METH-2 were found in lung cancer cell lines.

View Article: PubMed Central - PubMed

Affiliation: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK.

ABSTRACT
The antiangiogenic factor METH-2 (ADAMTS-8) was identified in a previous dual-channel cDNA microarray analysis to be at least two-fold under-represented in 85% (28 out of 33) of primary non-small-cell lung carcinomas (NSCLCs). This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed. Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs. DNA methylation analysis of the proximal promoter region of this gene revealed abnormal hypermethylation in 67% of the adenocarcinomas and 50% of squamous cell carcinomas, indicating that epigenetic mechanisms are involved in silencing this gene in NSCLC. No homozygous deletions of METH-2 were found in lung cancer cell lines. Allelic imbalance in METH-2 was assessed by an intronic single nucleotide polymorphism (SNP) assay and observed in 44% of informative primary samples. In conclusion, the downregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease.

Show MeSH
Related in: MedlinePlus