Expression of p16INK4a/p16alpha and p19ARF/p16beta is frequently altered in non-small cell lung cancer and correlates with p53 overexpression.
Vonlanthen, S Heighway, Jim Tschan, M P Borner, M M Altermatt, H J Kappeler, A Tobler, A Fey, M F Thatcher, Nick Yarbrough, W G
Vonlanthen, S
Heighway, Jim
Tschan, M P
Borner, M M
Altermatt, H J
Kappeler, A
Tobler, A
Fey, M F
Thatcher, Nick
Yarbrough, W G
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Abstract
The CDKN2 locus expresses two different mRNA transcripts, designated alpha and beta. The protein product of the alpha transcript is the cell cycle inhibitor and tumour suppressor p16INK4a. The beta transcript is translated in an alternate reading frame (ARF) and in humans encodes a 15 kDa protein (p19ARF). Immunohistochemical and Western analysis of p16INK4a has shown that the protein is downregulated in a significant number of tumours, but less is known on the expression of the p19ARF. We have examined the expression of p16INK4a and p19ARF in resectable non-small cell lung cancer (NSCLC) by immunostaining (n=49) and multiplex RT-PCR (n=28). In order to investigate the mechanism responsible for p16INK4a downregulation, exon 1alpha methylation was analysed in a PCR-based assay. Of 49 tumours examined by immunostaining, 24 and 20 tumours expressed p16INK4a and p19ARF at nil to low levels, respectively. p19ARF was localized primarily to the nuclei of tumour cells, but was also seen to varying degrees in nuclei of lymphocytes, chondrocytes, fibroblasts, and epithelial cells. No tumour with normal p16INK4a had decreased p19ARF expression. Among 16 tumours with nil to low p16INK4a expression, 11 tumours exhibited full methylation of at least one site within exon 1alpha and these tumours showed normal p19ARF expression. In contrast, no methylation of exon 1alpha was observed in five tumours which also lacked p19ARF. In normal lung, p16INK4a and p19ARF were not expressed at detectable levels, the multiplex RT-PCR results were balanced, and sites within exon 1alpha were strongly methylated. In tumours, imbalanced multiplex RT-PCR data (p16INK4a
Description
Date
1998-11-26
Publisher
Keywords
Cancer DNA
Cancer Proteins
Cancer RNA
Lung Cancer
Cultured Tumour Cells
Tumour Suppressor Protein p14ARF
Tumour Suppressor Protein p53
Cancer Proteins
Cancer RNA
Lung Cancer
Cultured Tumour Cells
Tumour Suppressor Protein p14ARF
Tumour Suppressor Protein p53
Type
Article
Citation
Expression of p16INK4a/p16alpha and p19ARF/p16beta is frequently altered in non-small cell lung cancer and correlates with p53 overexpression. 1998, 17 (21):2779-85 Oncogene