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. 1995 Jan;71(1):25–29. doi: 10.1038/bjc.1995.6

Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free patients.

J Harney 1, D M Murphy 1, M Jones 1, C Mothersill 1
PMCID: PMC2033449  PMID: 7819043

Abstract

An explant culture technique was used to culture normal urothelium from patients with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Cell cultures were examined for expression of p53 using the monoclonal antibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also showed more rapid proliferation in vitro when compared with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766). None of these urothelial specimens was observed to express p53 when paraffin-embedded preparations were stained with p53-D07 antibody prior to culture. The rate of cellular proliferation in this subgroup did not differ from that of normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle-invasive TCC specimens were also evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients with TCC and in proliferating cultures from a significant subgroup of patients without malignant disease. Increased p53 expression in normal cultured urothelial cells from patients with bladder cancer implies a global change in the mechanisms controlling urothelial cell division. This may represent an early step in the pathway to carcinogenesis.

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Selected References

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  1. Barnes D. M., Hanby A. M., Gillett C. E., Mohammed S., Hodgson S., Bobrow L. G., Leigh I. M., Purkis T., MacGeoch C., Spurr N. K. Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet. 1992 Aug 1;340(8814):259–263. doi: 10.1016/0140-6736(92)92354-i. [DOI] [PubMed] [Google Scholar]
  2. Cohen J. J. Apoptosis. Immunol Today. 1993 Mar;14(3):126–130. doi: 10.1016/0167-5699(93)90214-6. [DOI] [PubMed] [Google Scholar]
  3. Esrig D., Spruck C. H., 3rd, Nichols P. W., Chaiwun B., Steven K., Groshen S., Chen S. C., Skinner D. G., Jones P. A., Cote R. J. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer. Am J Pathol. 1993 Nov;143(5):1389–1397. [PMC free article] [PubMed] [Google Scholar]
  4. Farsund T., Hoestmark J. G., Laerum O. D. Relation between flow cytometric DNA distribution and pathology in human bladder cancer. A report on 69 cases. Cancer. 1984 Nov 1;54(9):1771–1777. doi: 10.1002/1097-0142(19841101)54:9<1771::aid-cncr2820540904>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  5. Fujimoto K., Yamada Y., Okajima E., Kakizoe T., Sasaki H., Sugimura T., Terada M. Frequent association of p53 gene mutation in invasive bladder cancer. Cancer Res. 1992 Mar 15;52(6):1393–1398. [PubMed] [Google Scholar]
  6. Furihata M., Inoue K., Ohtsuki Y., Hashimoto H., Terao N., Fujita Y. High-risk human papillomavirus infections and overexpression of p53 protein as prognostic indicators in transitional cell carcinoma of the urinary bladder. Cancer Res. 1993 Oct 15;53(20):4823–4827. [PubMed] [Google Scholar]
  7. Gannon J. V., Greaves R., Iggo R., Lane D. P. 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. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Habuchi T., Ogawa O., Kakehi Y., Ogura K., Koshiba M., Sugiyama T., Yoshida O. Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. J Urol. 1992 Nov;148(5):1595–1599. doi: 10.1016/s0022-5347(17)36977-x. [DOI] [PubMed] [Google Scholar]
  9. Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  12. Jones R. F., Matuszyk J., Debiec-Rychter M., Wang C. Y. Mutation and altered expression of p53 genes in experimental rat bladder tumor cells. Mol Carcinog. 1994 Feb;9(2):95–104. doi: 10.1002/mc.2940090207. [DOI] [PubMed] [Google Scholar]
  13. Kaklamanis L., Gatter K. C., Mortensen N., Baigrie R. J., Heryet A., Lane D. P., Harris A. L. p53 expression in colorectal adenomas. Am J Pathol. 1993 Jan;142(1):87–93. [PMC free article] [PubMed] [Google Scholar]
  14. Kastan M. B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed] [Google Scholar]
  15. Kawasaki Y., Monden T., Morimoto H., Murotani M., Miyoshi Y., Kobayashi T., Shimano T., Mori T. Immunohistochemical study of p53 expression in microwave-fixed, paraffin-embedded sections of colorectal carcinoma and adenoma. Am J Clin Pathol. 1992 Feb;97(2):244–249. doi: 10.1093/ajcp/97.2.244. [DOI] [PubMed] [Google Scholar]
  16. Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
  17. Lipponen P. K. Over-expression of p53 nuclear oncoprotein in transitional-cell bladder cancer and its prognostic value. Int J Cancer. 1993 Feb 1;53(3):365–370. doi: 10.1002/ijc.2910530304. [DOI] [PubMed] [Google Scholar]
  18. Mothersill C., Cusack A., MacDonnell M., Hennessy T. P., Seymour C. B. Differential response of normal and tumour oesophageal explant cultures to radiation. Acta Oncol. 1988;27(3):275–280. doi: 10.3109/02841868809093537. [DOI] [PubMed] [Google Scholar]
  19. Mothersill C., Seymour C. B., Harney J., Hennessy T. P. High levels of stable p53 protein and the expression of c-myc in cultured human epithelial tissue after cobalt-60 irradiation. Radiat Res. 1994 Mar;137(3):317–322. [PubMed] [Google Scholar]
  20. Ramel S., Reid B. J., Sanchez C. A., Blount P. L., Levine D. S., Neshat K., Haggitt R. C., Dean P. J., Thor K., Rabinovitch P. S. Evaluation of p53 protein expression in Barrett's esophagus by two-parameter flow cytometry. Gastroenterology. 1992 Apr;102(4 Pt 1):1220–1228. [PubMed] [Google Scholar]
  21. Rivas C. I., Wisniewski D., Strife A., Perez A., Lambek C., Bruno S., Darzynkiewicz Z., Clarkson B. Constitutive expression of p53 protein in enriched normal human marrow blast cell populations. Blood. 1992 Apr 15;79(8):1982–1986. [PubMed] [Google Scholar]
  22. Sarkis A. S., Dalbagni G., Cordon-Cardo C., Zhang Z. F., Sheinfeld J., Fair W. R., Herr H. W., Reuter V. E. Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst. 1993 Jan 6;85(1):53–59. doi: 10.1093/jnci/85.1.53. [DOI] [PubMed] [Google Scholar]
  23. Sidransky D., Messing E. Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors. Urol Clin North Am. 1992 Nov;19(4):629–639. [PubMed] [Google Scholar]
  24. Sidransky D., Von Eschenbach A., Tsai Y. C., Jones P., Summerhayes I., Marshall F., Paul M., Green P., Hamilton S. R., Frost P. Identification of p53 gene mutations in bladder cancers and urine samples. Science. 1991 May 3;252(5006):706–709. doi: 10.1126/science.2024123. [DOI] [PubMed] [Google Scholar]
  25. Spruck C. H., 3rd, Rideout W. M., 3rd, Olumi A. F., Ohneseit P. F., Yang A. S., Tsai Y. C., Nichols P. W., Horn T., Hermann G. G., Steven K. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. Cancer Res. 1993 Mar 1;53(5):1162–1166. [PubMed] [Google Scholar]
  26. Werness B. A., Levine A. J., Howley P. M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. doi: 10.1126/science.2157286. [DOI] [PubMed] [Google Scholar]
  27. Wright C., Mellon K., Johnston P., Lane D. P., Harris A. L., Horne C. H., Neal D. E. Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer. 1991 Jun;63(6):967–970. doi: 10.1038/bjc.1991.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

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