Skip to main content
Log in

WAF1/CIP1 protein expression in human breast tumors

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

WAF1/CIP1 is a cyclin-dependent kinase inhibitor which isdirectly induced by p53 and negatively controls cellproliferation. To test the hypothesis that increased levelsof WAF1 would be associated with a lowerS-phase fraction and better prognosis, WAF1 protein wasassessed by immunohistochemistry (IHC) in 115 node-negative humanbreast tumors, and results were correlated with establishedprognostic factors and clinical outcome. Nuclear staining wasobserved in malignant cells in 43% of tumors.In most (90%) of the positive tumors, theproportion of cells staining for WAF1 was low(< 10%). WAF1 was not detected in thecytoplasm, or in non-malignant epithelium. Contrary to expectations,the accumulation of p53 protein, a surrogate markerof p53 inactivation, was weakly but positively associatedwith WAF1 expression (p=0.05). Surprisingly, therewas no significant correlation with S-phase fraction, ERor PgR status, tumor size, age, ploidy, nucleargrade, or survival.

Conclusion: WAF1 expression is found inthe nuclei of a small fraction of cellsin human breast tumors. WAF1 status is notsignificantly associated with cell proliferation, other established prognosticfactors, or clinical outcome.

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. Osborne CK, Yochmowitz MG, Knight WA, McGuire WL: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46: 2884–2888, 1980

    Google Scholar 

  2. Lowe SW, Ruley HE, Jacks, T, Housman DE: p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74: 957–967, 1993

    Google Scholar 

  3. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M: Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352: 345–347, 1991

    Google Scholar 

  4. El-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Khon KW, Elledge SJ, Kinzler KW, Vogelstein B: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54: 1169–1174, 1994

    Google Scholar 

  5. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817–825, 1993

    Google Scholar 

  6. Xiong Y, Zhang H, Beach D: Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev 7: 1572–1583, 1993

    Google Scholar 

  7. 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 75: 805–816, 1993

    Google Scholar 

  8. Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D: Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res 54: 3391–3395, 1994

    Google Scholar 

  9. Shiohara M, El-Deiry WS, Wada M, Nakamaki T, Takeuchi S, Yang R, Chen DL, Vogelstein B, Koeffler HP: Absence of WAF1 mutations in a variety of human malignancies. Blood 84: 3781–3784, 1994

    Google Scholar 

  10. Allred DC, Clark G, Elledge R, Fuqua SAW, Brown RW, Chamness GC, Osborne CK, McGuire WL: Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85: 200–206, 1994

    Google Scholar 

  11. Wasielewski R, Von WM, Nolte M, Wilkens L, Georgii A: Effects of antigen retrieval by microwave heating in formalin-fixed tissue sections on a broad panel of antibodies. Histochemistry 102: 165–172, 1994

    Google Scholar 

  12. Levine AJ, Momand J, Finlay CA: The p53 tumour suppressor gene. Nature 351: 453–456, 1991

    Google Scholar 

  13. Momand J, Zambetti GP, Olson DC, George D, Levine AJ: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237–1345, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diab, S., Yu, YY., Hilsenbeck, S. et al. WAF1/CIP1 protein expression in human breast tumors. Breast Cancer Res Treat 43, 99–103 (1997). https://doi.org/10.1023/A:1005752829260

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005752829260

Navigation