Skip to main content
Log in

Infrequent but significant p21/WAF1/CIP1 gene alteration in synchronous or metachronous transitional cell carcinoma

  • Reports
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

p53 inducible cyclin dependent kinase inhibitor, p21/WAF1/CIP1(p21), played a pivotal role for G1 arrest when cells received genotoxic stimuli. p21 could be a putative tumor suppressor gene, since its dysfunction may lead to accumulation of genomic alteration. We investigated the p21 and p53 status using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemical analyses, in eight patients who had synchronous or metachronous urothelial tumors. Loss of heterozygosity (LOH) of p21 gene was detected in one coincidental tumor in one case. p21 positive cells were detected by immuno-histochemical staining in all tumors in one case, and in one coincidental tumor in two cases. Among p21 positive cells in these three cases, no p53 mutations were detected, whereas no p21 positive cells were detected in other cases with a p53 mutation. These findings suggested that in transitional cell carcinoma (TCC) p21 gene mutation is infrequent like the p53 gene mutation, but that LOH might be important in the inactivation of p21.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. El-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817–825.

    Google Scholar 

  2. El-Deiry WS, Tokino T, Waldman T, et al. Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res 1995; 55: 2910–2919.

    Google Scholar 

  3. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993; 75: 805–816.

    Google Scholar 

  4. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature 1993; 366: 701–704.

    Google Scholar 

  5. Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994; 369: 574–578.

    Google Scholar 

  6. El-Deiry WS, Harper JW, O'Connor PM, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994; 54: 1169–1174.

    Google Scholar 

  7. Shiohara M, El-Deiry WS, Wada M, et al. Absence of WAF1 mutations in a variety of human malignancies. Blood 1994; 84: 3781–3784.

    Google Scholar 

  8. Li YJ, Laurent-Puig P, Salmon RJ, Thomas G, Hamelin R. Polymorphisms and probable lack of mutation in the WAF1- CIP1 gene in colorectal cancer. Oncogene 1995 ; 10: 599–601.

    Google Scholar 

  9. Bhatia K, Fan S, Spangler G, Weintraub M, O'Connor PM, Judde JG, Magrath I. A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma. Cancer Res 1995; 55: 1431–1435.

    Google Scholar 

  10. Wolf H, Hojgaard K. Urothelial dysplasia concomitant with bladder tumours as a determinant factor for future new occurrences. Lancet 1983; 2: 134–136.

    Google Scholar 

  11. Harris AL, Neal DE. Bladder cancer-field versus clonal origin. New Engl J Med 1992; 326: 759–761.

    Google Scholar 

  12. Sidransky D, Frost P, Eschenbach AV, Oyasu R, Preisinger AC, Vogelstein B. Clonal origin of bladder cancer. N Engl J Med 1992; 326: 737–740.

    Google Scholar 

  13. Lunec J, Challen C, Wright C, Mellon K, Neal DE. c-erbB-2 amplification and identical p53 mutations in concomitant transitional carcinomas of renal pelvis and urinary bladder. Lancet 1992; 339: 439–440.

    Google Scholar 

  14. Habuchi T, Takahashi R, Yamada H, Kakehi Y, Sugiyama T, Yoshida O. Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet 1993; 342: 1087–1088.

    Google Scholar 

  15. Spruck III CH, Ohneseit PF, Gonzalez-Zulueta M, et al. Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 1994; 54: 784–788.

    Google Scholar 

  16. Suzuki Y, Tamura G. Mutations of the p5 3 gene in carcinomas of the urinary system. Acta Pathlogica Japonica 1993; 43: 745–750.

    Google Scholar 

  17. Miyao N, Tsai YC, Lerner SP, et al. Role of chromosome 9 in human bladder cancer. Cancer Res 1993; 53: 4066–4070.

    Google Scholar 

  18. 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; 52: 1393–1398.

    Google Scholar 

  19. World Health Organization. Histological Typing of Urinary Bladder Tumors. International Histological Classification of Tumors, no 10. {dy1973}.

  20. Kawasaki T, Tomita Y, Watanabe R, Tanikawa T, Kumanishi T, Sato S. mRNA and protein expression of p53 mutations in human bladder cancer cell lines. Cancer Lett 1994; 82: 113–121.

    Google Scholar 

  21. Chedid M, Michieli P, Lengel C, Huppi K, Givol D. A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53-inducible gene WAF1/CIP1. Oncogene 1994; 9: 3021–3024.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kawasaki, T., Tomita, Y., Bilim, V. et al. Infrequent but significant p21/WAF1/CIP1 gene alteration in synchronous or metachronous transitional cell carcinoma. Apoptosis 1, 69–74 (1996). https://doi.org/10.1007/BF00142080

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00142080

Key words

Navigation