Abstract
p53 alterations were studied in a group of 22 primary squamous cell carcinomas (SCC) of the head and neck and in 10 cell lines derived from SCC. Positive immunohistochemical detection of p53 was accomplished in 10 of 22 primary tumors and in 7 of 10 SCC cell lines. Loss of heterozygosity of chromosome 17p, were the p53 gene is localized, was seen in five of seven SCC lines studied. DNA sequencing of the p53 gene of these five cell lines that had lost one allele showed p53 mutations in the remaining allele. In addition, from six primary SCC that exhibited loss of heterozygosity of chromosome 17p, three showed missense mutations of the p53 gene. The mutations of primary tumors and SCC cell lines were scattered in the midregion of the gene, affecting codons 151, 155, 174, 194, 220, 248, and 273. Five of these mutations modified guanine residues, a phenomenon that has been associated with the effect of carcinogens contained in tobacco smoke. Collectively these data show that approximately 50% of primary tumors and cell lines derived from SCC of the head and neck showed abnormalities of the p53 gene. In addition, it is of interest to note that the most invasive cell lines, as determined in an in vivo assay using xenotransplantation of tumor cells into denuded rat tracheal grafts, exhibited the most intense staining. Similarly, of five very advanced primary tumors, four showed intense p53 immunostain. These observations support the evidence that alterations in this tumor suppressor gene could be related to late events in tumor progression.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennett W. P., Hollstein M. C., He A., Zhu S. M., Resau J. H., Trump B. F., Metcalf R. A., Welsh J. A., Midgley C., Lane D. P. Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. Oncogene. 1991 Oct;6(10):1779–1784. [PubMed] [Google Scholar]
- Berenson J. R., Yang J., Mickel R. A. Frequent amplification of the bcl-1 locus in head and neck squamous cell carcinomas. Oncogene. 1989 Sep;4(9):1111–1116. [PubMed] [Google Scholar]
- Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
- Boynton R. F., Blount P. L., Yin J., Brown V. L., Huang Y., Tong Y., McDaniel T., Newkirk C., Resau J. H., Raskind W. H. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3385–3388. doi: 10.1073/pnas.89.8.3385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brash D. E., Rudolph J. A., Simon J. A., Lin A., McKenna G. J., Baden H. P., Halperin A. J., Pontén J. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124–10128. doi: 10.1073/pnas.88.22.10124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1038/350429a0. [DOI] [PubMed] [Google Scholar]
- Caamano J., Ruggeri B., Momiki S., Sickler A., Zhang S. Y., Klein-Szanto A. J. Detection of p53 in primary lung tumors and nonsmall cell lung carcinoma cell lines. Am J Pathol. 1991 Oct;139(4):839–845. [PMC free article] [PubMed] [Google Scholar]
- Caron de Fromentel C., Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1–15. doi: 10.1002/gcc.2870040102. [DOI] [PubMed] [Google Scholar]
- Ciechanover A., DiGiuseppe J. A., Bercovich B., Orian A., Richter J. D., Schwartz A. L., Brodeur G. M. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):139–143. doi: 10.1073/pnas.88.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1136/bmj.2.6051.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
- Field J. K., Spandidos D. A., Malliri A., Gosney J. R., Yiagnisis M., Stell P. M. Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck. Br J Cancer. 1991 Sep;64(3):573–577. doi: 10.1038/bjc.1991.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gusterson B. A., Anbazhagan R., Warren W., Midgely C., Lane D. P., O'Hare M., Stamps A., Carter R., Jayatilake H. Expression of p53 in premalignant and malignant squamous epithelium. Oncogene. 1991 Oct;6(10):1785–1789. [PubMed] [Google Scholar]
- Hollstein M. C., Metcalf R. A., Welsh J. A., Montesano R., Harris C. C. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9958–9961. doi: 10.1073/pnas.87.24.9958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollstein M. C., Peri L., Mandard A. M., Welsh J. A., Montesano R., Metcalf R. A., Bak M., Harris C. C. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. Cancer Res. 1991 Aug 1;51(15):4102–4106. [PubMed] [Google Scholar]
- Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
- Hsu I. C., Metcalf R. A., Sun T., Welsh J. A., Wang N. J., Harris C. C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. doi: 10.1038/350427a0. [DOI] [PubMed] [Google Scholar]
- Iggo R., Gatter K., Bartek J., Lane D., Harris A. L. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. doi: 10.1016/0140-6736(90)90801-b. [DOI] [PubMed] [Google Scholar]
- Ishitoya J., Toriyama M., Oguchi N., Kitamura K., Ohshima M., Asano K., Yamamoto T. Gene amplification and overexpression of EGF receptor in squamous cell carcinomas of the head and neck. Br J Cancer. 1989 Apr;59(4):559–562. doi: 10.1038/bjc.1989.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein-Szanto A. J., Baba M., Trono D., Obara T., Resau J., Trump B. F. Epidermoid metaplasias of xenotransplanted human tracheobronchial epithelium. Carcinogenesis. 1986 Jun;7(6):987–994. doi: 10.1093/carcin/7.6.987. [DOI] [PubMed] [Google Scholar]
- Kondoleon S., Vissing H., Luo X. Y., Magenis R. E., Kellogg J., Litt M. A hypervariable RFLP on chromosome 17p13 is defined by an arbitrary single copy probe p144-D6 [HGM9 No. D17S34]. Nucleic Acids Res. 1987 Dec 23;15(24):10605–10605. doi: 10.1093/nar/15.24.10605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lammie G. A., Fantl V., Smith R., Schuuring E., Brookes S., Michalides R., Dickson C., Arnold A., Peters G. D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. Oncogene. 1991 Mar;6(3):439–444. [PubMed] [Google Scholar]
- Lehman T. A., Bennett W. P., Metcalf R. A., Welsh J. A., Ecker J., Modali R. V., Ullrich S., Romano J. W., Appella E., Testa J. R. p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res. 1991 Aug 1;51(15):4090–4096. [PubMed] [Google Scholar]
- Maestro R., Dolcetti R., Gasparotto D., Doglioni C., Pelucchi S., Barzan L., Grandi E., Boiocchi M. High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx. Oncogene. 1992 Jun;7(6):1159–1166. [PubMed] [Google Scholar]
- Marshall C. J. Tumor suppressor genes. Cell. 1991 Jan 25;64(2):313–326. doi: 10.1016/0092-8674(91)90641-b. [DOI] [PubMed] [Google Scholar]
- Mercer W. E., Baserga R. Expression of the p53 protein during the cell cycle of human peripheral blood lymphocytes. Exp Cell Res. 1985 Sep;160(1):31–46. doi: 10.1016/0014-4827(85)90233-2. [DOI] [PubMed] [Google Scholar]
- Momiki S., Baba M., Caamano J., Iizasa T., Nakajima M., Yamaguchi Y., Klein-Szanto A. In vivo and in vitro invasiveness of human lung carcinoma cell lines. Invasion Metastasis. 1991;11(2):66–75. [PubMed] [Google Scholar]
- Motokura T., Bloom T., Kim H. G., Jüppner H., Ruderman J. V., Kronenberg H. M., Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512–515. doi: 10.1038/350512a0. [DOI] [PubMed] [Google Scholar]
- Nakamura Y., Ballard L., Leppert M., O'Connell P., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pYNZ22) on chromosome 17p [D17S30]. Nucleic Acids Res. 1988 Jun 24;16(12):5707–5707. doi: 10.1093/nar/16.12.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
- Ogden G. R., Kiddie R. A., Lunny D. P., Lane D. P. Assessment of p53 protein expression in normal, benign, and malignant oral mucosa. J Pathol. 1992 Apr;166(4):389–394. doi: 10.1002/path.1711660411. [DOI] [PubMed] [Google Scholar]
- Osipovich O. A., Misuno N. I., Kolesnikova T. S., Sudarikov A. B., Voitenok N. N. The difference in p53 antioncogene transcription in human monocytes and lymphocytes. Oncogene. 1992 Mar;7(3):549–552. [PubMed] [Google Scholar]
- Pierceall W. E., Mukhopadhyay T., Goldberg L. H., Ananthaswamy H. N. Mutations in the p53 tumor suppressor gene in human cutaneous squamous cell carcinomas. Mol Carcinog. 1991;4(6):445–449. doi: 10.1002/mc.2940040606. [DOI] [PubMed] [Google Scholar]
- Ronen D., Rotter V., Reisman D. Expression from the murine p53 promoter is mediated by factor binding to a downstream helix-loop-helix recognition motif. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4128–4132. doi: 10.1073/pnas.88.10.4128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruggeri B., DiRado M., Zhang S. Y., Bauer B., Goodrow T., Klein-Szanto A. J. Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1013–1017. doi: 10.1073/pnas.90.3.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rumsby G., Carter R. L., Gusterson B. A. Low incidence of ras oncogene activation in human squamous cell carcinomas. Br J Cancer. 1990 Mar;61(3):365–368. doi: 10.1038/bjc.1990.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakai E., Tsuchida N. Most human squamous cell carcinomas in the oral cavity contain mutated p53 tumor-suppressor genes. Oncogene. 1992 May;7(5):927–933. [PubMed] [Google Scholar]
- Schipper J. H., Frixen U. H., Behrens J., Unger A., Jahnke K., Birchmeier W. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991 Dec 1;51(23 Pt 1):6328–6337. [PubMed] [Google Scholar]
- Schmidt W., Popham R. E. The role of drinking and smoking in mortality from cancer and other causes in male alcoholics. Cancer. 1981 Mar 1;47(5):1031–1041. doi: 10.1002/1097-0142(19810301)47:5<1031::aid-cncr2820470534>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- Schuuring E., Verhoeven E., Mooi W. J., Michalides R. J. Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene. 1992 Feb;7(2):355–361. [PubMed] [Google Scholar]
- Vogelstein B., Kinzler K. W. Carcinogens leave fingerprints. Nature. 1992 Jan 16;355(6357):209–210. doi: 10.1038/355209a0. [DOI] [PubMed] [Google Scholar]
- Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
- Wynder E. L., Stellman S. D. Comparative epidemiology of tobacco-related cancers. Cancer Res. 1977 Dec;37(12):4608–4622. [PubMed] [Google Scholar]
- Yin X. Y., Donovan-Peluso M., Whiteside T. L., Johnson J. T., Day R., Herberman R. B., Locker J. Gene amplification and gene dosage in cell lines derived from squamous cell carcinoma of the head and neck. Genes Chromosomes Cancer. 1991 Nov;3(6):443–454. doi: 10.1002/gcc.2870030606. [DOI] [PubMed] [Google Scholar]
- Zakut-Houri R., Bienz-Tadmor B., Givol D., Oren M. Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. EMBO J. 1985 May;4(5):1251–1255. doi: 10.1002/j.1460-2075.1985.tb03768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van den Heuvel S. J., van Laar T., Kast W. M., Melief C. J., Zantema A., van der Eb A. J. Association between the cellular p53 and the adenovirus 5 E1B-55kd proteins reduces the oncogenicity of Ad-transformed cells. EMBO J. 1990 Aug;9(8):2621–2629. doi: 10.1002/j.1460-2075.1990.tb07444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]