Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Mutational analysis of p51A/TAp63γ, a p53 homolog, in non-small cell lung cancer and breast cancer

Oncogene volume 18, pages 3761–3765 (1999)Cite this article

Abstract

p51, a novel family member of human p53, is a recently identified candidate tumor suppressor gene mapped at chromosome 3q28. Like p53, p51 was found to activate p21Waf1/Cip1 and to induce apoptosis. Since the DNA loss at 3q is reported in several cancers including non-small cell lung cancer (NSCLC), we screened for mutations in p51A (TAp63γ), an isoform of p51 with short C-terminal region, in 80 NSCLCs as well as 85 breast cancers by RT – PCR single strand conformation polymorphism (SSCP) analysis and DNA sequencing. In NSCLCs, p51 was expressed in most tumors at variable levels and we found three missense and one silent mutations: Gln31His (transactivation domain) in two tumors, Ala148Pro (DNA-binding domain) and Leu248Leu (DNA-binding domain). In the tumor with Ala148Pro or the silent mutation, only the mutant gene appeared to be expressed. The modified FASAY method to test the ability of yeast expressing p51A cDNA to grow in medium lacking histidine has revealed that Ala148Pro results in a loss of function, while Gln31His does not. In contrast to NSCLC, no mutation was observed in all 85 breast cancers by the similar method. Our results suggest that, because of infrequent mutation, p51 may not be a Knudson type tumor suppressor in most NSCLCs and breast cancers. Nevertheless, in at least a part of NSCLC, p51 may play a certain role in carcinogenesis in a tissue-specific manner.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Coles C, Condie A, Chetty U, Steel MC, Evans JH and Prosser J. . 1992 Cancer Res. 52: 5291–5298.

  • Di Como CJ, Gaiddon C and Prives C. . 1999 Mol. Cell. Biol. 19: 1438–1449.

  • Hollstein M, Sidransky D, Vogelstein B and Harris CC. . 1991 Science 253: 49–53.

  • Ichimiya S, Nimura Y, Kageyama H, Takada N, Sunahara M, Shishikura T, Nakamura Y, Sakiyama S, Seki N, Ohira M, Kaneko Y, McKeon F, Caput D and Nakagawara A. . 1999 Oncogene 18: 1061–1066.

  • Ishioka C, Frebourg T, Yan YX, Vidal M, Friend SH, Schmidt S and Iggo R. . 1993 Nature Genet. 5: 124–129.

  • Ishioka C, Englert C, Winge P, Yan Y-X, Engelstein M and Friend SH. . 1995 Oncogene 10: 1485–1492.

  • Japanese Breast Cancer Society. . 1989 Jpn. Surg. 19: 612–632.

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan J-C, Valent A, Minty A, Chalon P, Lelias J-M, Dumont X, Ferrara P, Mckeon F and Caput D. . 1997 Cell 90: 809–819.

  • Kishimoto Y, Murakami Y, Shiraishi M, Hayashi K and Sekiya T. . 1990 Cancer Res. 52: 4799–4804.

  • Levine AJ. . 1997 Cell 88: 323–331.

  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC and Vogelstein B. . 1989 Nature 342: 705–708.

  • Nishio M, Koshikawa T, Kuroishi T, Suyama M, Uchida K, Takagi Y, Washimi O, Sugiura T, Ariyoshi T, Takahashi T, Ueda R and Takahashi T. . 1996 J. Clin. Oncol. 14: 497–502.

  • Nomoto S, Haruki N, Kondo M, Konishi H, Takahashi T, Takahashi T and Takahashi T. . 1998 Cancer Res. 58: 1380–1383.

  • Orita M, Iwahara H, Kanazawa H, Hayashi K and Sekiya T. . 1989 Proc. Natl. Acad. Sci. USA 86: 2766–2770.

  • Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M and Ikawa S. . 1998 Nature Med. 4: 839–843.

  • Osborne RJ, Merlo RG, Mitsudomi T, Venesio T, Liscia SD, Cappa MPA, Chiba I, Takahashi T, Nau MM, Callahan R and Minna DJ. . 1991 Cancer Res. 51: 6194–6198.

  • Petersen I, Bujard M, Petersen S, Wolf G, Goeze A, Schwendel A, Langreck H, Gellert K, Reichel M, Just K, du Manior S, Cremer T, Dietel M and Ried T. . 1997 Cancer Res. 57: 2331–2335.

  • Sato S, Nakamura Y and Tsuchiya E. . 1994 Cancer Res. 54: 5652–5655.

  • Sunahara M, Ichimiya S, Nimura Y, Takada N, Sakiyama S, Sato Y, Todo S, Adachi W, Amano J and Nakagawara A. . 1998 Int. J. Oncol. 13: 319–323.

  • Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF and Minna JD. . 1989 Science 246: 491–494.

  • Takahashi H, Ichimiya S, Watanabe M, Furusato M, Wakui S, Yatani R, Aizawa S and Nakagawara A. . 1998 Cancer Res. 58: 2076–2077.

  • Yang C, Kaghad M, Wang Y, Gillet E, Fleming MD, Dotsch V, Andrews NC, Caput D and McKeon F. . 1998 Mol. Cell 2: 305–316.

Download references

Acknowledgements

The authors thank S Sakiyama and T Ozaki for reading manuscript, and A Morohashi for preparing RNA. The authors are also grateful to M Miyauchi, N Yamamoto, N Imanaka and M Matsumoto for providing tumor samples, M Suzuki and N Nakajima for encouragement and M Hirose and T Takenouchi for their help in the Chiba Cancer Center Tissue Bank. This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare for a New Comprehensive 10-Year Strategy for Cancer Control, Japan, and grants from Naito Foundation and Uehara Foundation. T Shishikura and M Takahashi are awardees of Research Resident Fellowship from the Foundation for the Promotion of Cancer Research, Japan.

Author information

Authors and Affiliations

  1. Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, 260-8717, Chiba, Japan

    Masao Sunahara, Tomotane Shishikura, Masato Takahashi, Naoyoshi Yamamoto & Akira Nakagawara

  2. First Department of Surgery, Hokkaido University School of Medicine, N15 W7, Kita-ku, Sapporo, 060-8638, Japan

    Masao Sunahara, Masato Takahashi & Satoru Todo

  3. Department of Surgery, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University, Japan

    Naoyoshi Yamamoto

  4. Division of Thoracic Surgery, Chiba Cancer Center, 662-2 Nitona, Chuoh-ku, 260-8717, Chiba, Japan

    Naoyoshi Yamamoto & Hideki Kimura

  5. Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-0872, Japan

    Shunsuke Kato & Chikashi Ishioka

  6. Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-0872, Japan

    Shuntaro Ikawa

  7. Department of Retroviral Regulation, Medical Research Division, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

    Yoji Ikawa

Authors
  1. Masao Sunahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomotane Shishikura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masato Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoru Todo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoyoshi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideki Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shunsuke Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chikashi Ishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shuntaro Ikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoji Ikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Akira Nakagawara
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sunahara, M., Shishikura, T., Takahashi, M. et al. Mutational analysis of p51A/TAp63γ, a p53 homolog, in non-small cell lung cancer and breast cancer. Oncogene 18, 3761–3765 (1999). https://doi.org/10.1038/sj.onc.1202972

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202972

Keywords

This article is cited by

Search

Advanced search

Quick links