The p53 status of cultured human premalignant oral keratinocytes

J. E. Burns, L. J. Clark, William Andrew Yeudall, R. Mitchell, K. Mackenzie, S. E. Chang, E. K. Parkinson

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.

Original languageEnglish (US)
Pages (from-to)591-595
Number of pages5
JournalBritish Journal of Cancer
Volume70
Issue number4
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

p53 Genes
Keratinocytes
Squamous Cell Carcinoma
Biopsy
DNA
Human papillomavirus 11
Human papillomavirus 6
Human papillomavirus 18
Human papillomavirus 16
Papilloma
Codon
Epithelium
Cell Culture Techniques
Research Personnel
Phenotype
Cell Line
Mutation
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Burns, J. E., Clark, L. J., Yeudall, W. A., Mitchell, R., Mackenzie, K., Chang, S. E., & Parkinson, E. K. (1994). The p53 status of cultured human premalignant oral keratinocytes. British Journal of Cancer, 70(4), 591-595. https://doi.org/10.1038/bjc.1994.356

The p53 status of cultured human premalignant oral keratinocytes. / Burns, J. E.; Clark, L. J.; Yeudall, William Andrew; Mitchell, R.; Mackenzie, K.; Chang, S. E.; Parkinson, E. K.

In: British Journal of Cancer, Vol. 70, No. 4, 01.01.1994, p. 591-595.

Research output: Contribution to journalArticle

Burns, JE, Clark, LJ, Yeudall, WA, Mitchell, R, Mackenzie, K, Chang, SE & Parkinson, EK 1994, 'The p53 status of cultured human premalignant oral keratinocytes', British Journal of Cancer, vol. 70, no. 4, pp. 591-595. https://doi.org/10.1038/bjc.1994.356
Burns, J. E. ; Clark, L. J. ; Yeudall, William Andrew ; Mitchell, R. ; Mackenzie, K. ; Chang, S. E. ; Parkinson, E. K. / The p53 status of cultured human premalignant oral keratinocytes. In: British Journal of Cancer. 1994 ; Vol. 70, No. 4. pp. 591-595.
@article{9580875971284b3bb1bf5c9f9d444451,
title = "The p53 status of cultured human premalignant oral keratinocytes",
abstract = "Around 60{\%} of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.",
author = "Burns, {J. E.} and Clark, {L. J.} and Yeudall, {William Andrew} and R. Mitchell and K. Mackenzie and Chang, {S. E.} and Parkinson, {E. K.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1038/bjc.1994.356",
language = "English (US)",
volume = "70",
pages = "591--595",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - The p53 status of cultured human premalignant oral keratinocytes

AU - Burns, J. E.

AU - Clark, L. J.

AU - Yeudall, William Andrew

AU - Mitchell, R.

AU - Mackenzie, K.

AU - Chang, S. E.

AU - Parkinson, E. K.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.

AB - Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.

UR - http://www.scopus.com/inward/record.url?scp=0028024760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028024760&partnerID=8YFLogxK

U2 - 10.1038/bjc.1994.356

DO - 10.1038/bjc.1994.356

M3 - Article

C2 - 7917902

AN - SCOPUS:0028024760

VL - 70

SP - 591

EP - 595

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

ER -