Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. Dec 1991; 64(6): 1076–1082.
PMCID: PMC1977874

Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer.

Abstract

The tumour suppressor gene p53 has been found to be mutated or inactivated at high frequency in several common human tumours. We have examined a series of exocrine pancreatic carcinomas for over-expression of mutant forms of p53 by immunohistochemistry with a panel of specific antibodies. We found immunodetectable p53 in 13 of 22 (60%) frozen pancreatic cancers and seven of 13 pancreatic cell lines. One of the antibodies, CM1, recognises p53 in formalin-fixed, paraffin-embedded archival material and using this reagent we found immunodetectable p53 in 28 of 124 (23%) pancreatic cancers. We have successfully demonstrated the presence of point mutations by direct sequencing of genomic DNA extracted from archival tissue showing CM1 immunoreactivity. We conclude that p53 activation is an important event in human pancreatic tumorigenesis and that the CM1 antibody can detect a proportion of cases of overexpression of mutant p53 in archival pathological material.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JK, Hamilton S, Vogelstein B. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990 Dec 1;50(23):7717–7722. [PubMed]
  • Banks L, Matlashewski G, Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. [PubMed]
  • Bartek J, Iggo R, Gannon J, Lane DP. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene. 1990 Jun;5(6):893–899. [PubMed]
  • Bártek J, Bártková J, Vojtesek B, Stasková Z, Lukás J, Rejthar A, Kovarík J, Midgley CA, Gannon JV, Lane DP. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene. 1991 Sep;6(9):1699–1703. [PubMed]
  • Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR. Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol. 1991 Feb;163(2):111–116. [PubMed]
  • Bos JL. ras oncogenes in human cancer: a review. Cancer Res. 1989 Sep 1;49(17):4682–4689. [PubMed]
  • Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991 Apr 4;350(6317):429–431. [PubMed]
  • Buchman VL, Chumakov PM, Ninkina NN, Samarina OP, Georgiev GP. A variation in the structure of the protein-coding region of the human p53 gene. Gene. 1988 Oct 30;70(2):245–252. [PubMed]
  • Chiba I, Takahashi T, Nau MM, D'Amico D, Curiel DT, Mitsudomi T, Buchhagen DL, Carbone D, Piantadosi S, Koga H, et al. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603–1610. [PubMed]
  • Ciardiello F, McGeady ML, Kim N, Basolo F, Hynes N, Langton BC, Yokozaki H, Saeki T, Elliott JW, Masui H, et al. Transforming growth factor-alpha expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras protooncogene but not by the c-neu protooncogene, and overexpression of the transforming growth factor-alpha complementary DNA leads to transformation. Cell Growth Differ. 1990 Sep;1(9):407–420. [PubMed]
  • Doll R, Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J. 1976 Dec 25;2(6051):1525–1536. [PMC free article] [PubMed]
  • Gannon JV, Greaves R, Iggo R, Lane DP. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. [PMC free article] [PubMed]
  • Hall PA, Hughes CM, Staddon SL, Richman PI, Gullick WJ, Lemoine NR. The c-erb B-2 proto-oncogene in human pancreatic cancer. J Pathol. 1990 Jul;161(3):195–200. [PubMed]
  • Hinds PW, Finlay CA, Quartin RS, Baker SJ, Fearon ER, Vogelstein B, Levine AJ. Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the "hot spot" mutant phenotypes. Cell Growth Differ. 1990 Dec;1(12):571–580. [PubMed]
  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. [PubMed]
  • Iggo R, Gatter K, Bartek J, Lane D, Harris AL. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. [PubMed]
  • Klöppel G, Maillet B. Classification and staging of pancreatic nonendocrine tumors. Radiol Clin North Am. 1989 Jan;27(1):105–119. [PubMed]
  • Lemoine NR, Hall PA. Growth factors and oncogenes in pancreatic cancer. Baillieres Clin Gastroenterol. 1990 Dec;4(4):815–832. [PubMed]
  • Lemoine NR, Mayall ES, Wyllie FS, Williams ED, Goyns M, Stringer B, Wynford-Thomas D. High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene. 1989 Feb;4(2):159–164. [PubMed]
  • Malkin D, Li FP, Strong LC, Fraumeni JF, Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233–1238. [PubMed]
  • MacMahon B. Risk factors for cancer of the pancreas. Cancer. 1982 Dec 1;50(11 Suppl):2676–2680. [PubMed]
  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. [PubMed]
  • Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, Lane DP. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. [PMC free article] [PubMed]
  • Shibata D, Capella G, Perucho M. Mutational activation of the c-K-ras gene in human pancreatic carcinoma. Baillieres Clin Gastroenterol. 1990 Mar;4(1):151–169. [PubMed]
  • Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990 Dec 20;348(6303):747–749. [PubMed]
  • Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF, Minna JD. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989 Oct 27;246(4929):491–494. [PubMed]
  • Vogelstein B. Cancer. A deadly inheritance. Nature. 1990 Dec 20;348(6303):681–682. [PubMed]
  • Wade-Evans A, Jenkins JR. Precise epitope mapping of the murine transformation-associated protein, p53. EMBO J. 1985 Mar;4(3):699–706. [PMC free article] [PubMed]
  • Williamson RC. Pancreatic cancer: the greatest oncological challenge. Br Med J (Clin Res Ed) 1988 Feb 13;296(6620):445–446. [PMC free article] [PubMed]
  • Wright PA, Lemoine NR, Goretzki PE, Wyllie FS, Bond J, Hughes C, Röher HD, Williams ED, Wynford-Thomas D. Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. Oncogene. 1991 Sep;6(9):1693–1697. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...