Abstract
p73 is a candidate tumor suppressor gene with substantial DNA and protein homology to the p53 tumor suppressor gene. We have investigated two hypotheses: (a) p73 is mutated in diverse types of human cancer, and (b) p73 is functionally redundant with p53 in carcinogenesis so that mutations would be exclusive in these two genes. The entire coding region and intronic splice junctions of p73 were examined in 54 cancer cell lines. Three lung cancer cell lines contained mutations that affected the amino acid sequence. One amino acid substitution was in a region with homology to the specific DNA binding region of p53 and two microdeletions were outside the region of homology. Two of the cell lines with p73 mutations also carried p53 mutations. Although our results are inconsistent with the two hypotheses tested, p73 mutations may contribute infrequently to the molecular pathogenesis of human lung cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- LOH:
-
loss of heterozygosity
- NSCLC:
-
non-small cell lung cancer
- SCLC:
-
small cell lung cancer
- HCC:
-
hepatocellular carcinoma
- BAC:
-
bacterial artificial chromosome
References
Bodner SM, Minna JD, Jensen SM, D'Amico D, Carbone D, Mitsudomi T, Fedorko J, Buchhagen DL, Nau MM, Gazdar AF, et al. (1992). . Oncogene 7: 743–749.
Caamano J, Zhang SY, Rosvold EA, Bauer B and Klein-Szanto AJ. (1993). . Am. J. Pathol. 142: 1131–1139.
El Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B. . 1993 Cell 75: 817–825.
Greenblatt MS, Bennett WP, Hollstein M and Harris CC. . 1994 Cancer Res. 54: 4855–4878.
Greenblatt MS, Grollman AP and Harris CC. . 1996 Cancer Res. 56: 2130–2136.
Hagiwara K and Harris CC. . 1996 Nucl. Acids Res. 24: 2460–2461.
Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ. . 1993 Cell. 75: 805–816.
Hollstein M, Metcalf RA, Welsh J, Montesano R and Harris CC. (1990). . Proc. Natl. Acad. Sci. USA. 87: 9958–9961.
Hsu IC, Tokiwa T, Bennett W, Metcalf RA, Welsh JA, Sun T and Harris CC. (1993). . Carcinogenesis 14: 987–992.
Jost CA, Marin MC and Kaelin Jr WG. . 1997 Nature 389: 191–194.
Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F and Caput D. . 1997 Cell 90: 809–819.
Kastrinakis WV, Ramchurren N, Rieger KM, Hess DT, Loda M, Steele G and Summerhayes IC. (1995). . Oncogene 11: 647–652.
Kovach JS, McGovern RM, Cassady JD, Swanson SK, Wold LE, Vogelstein B and Sommer SS. (1991). . J. Natl. Cancer Inst. 83: 1004–1009.
Lehman TA, Bennett WP, Metcalf RA, Reddel R, Welsh JA, Ecker J, Modali RV, Ullrich S, Romano JW, Appella E, Testa JR, Gerwin BI and Harris CC. (1991). . Cancer Res. 51: 4090–4096.
Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI and Liu W. . 1998 Cancer Res. 58: 2347–2349.
Nomoto S, Haruki N, Kondo M, Konishi H and Takahashi T. . 1998 Cancer Res. 58: 1380–1383.
Metcalf RA, Welsh JA, Bennett WP, Seddon MB, Lehman TA, Pelin K, Linnainmaa K, Tammilehto L, Mattson K, Gerwin BI and Harris CC. (1992). . Cancer Res. 52: 2610–2615.
Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, et al. (1992). . Oncogene 7: 171–180.
Murakami Y, Hayashi K and Sekiya T. (1991). . Cancer Res. 51: 3356–3361.
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.
Orita M, Suzuki Y, Sekiya T and Hayashi K. . 1989 Genomics 5: 874–879.
Peinado MA, Fernandez-Renart M, Capella G, Wilson L and Perucho M. (1993). . Int. J. Oncol. 2: 123–134.
Rodrigues NR, Rowan A, Smith MEF, Kerr IB, Bodmer WF, Gannon JV and Lane DP. (1990). . Proc. Natl. Acad. Sci. USA. 87: 7555–7559.
Ruggeri B, Zhang SY, Caamano J, DiRado M, Flynn SD and Klein-Szanto AJ. (1992). . Oncogene 7: 1503–1511.
Russel SJ, Ye YW, Waber PG, Shuford M, Schold Jr SC and Nisen PD. (1995). . Cancer 75: 1339–1342.
Somers KD, Merrick MA, Lopez ME, Incognito LS, Schechter GL and Casey G. (1992). . Cancer Res. 52: 5997–6000.
Takahashi H, Ichimiya S, Nimura Y, Watanabe M, Furusato M, Wakui S, Yatani R, Aizawa S and Nakagawara A. . 1998 Cancer Res. 58: 2076–2077.
Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R and Beach D. . 1993 Nature 366: 701–704.
Acknowledgements
We thank D Dudek for her editorial assistance.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshikawa, H., Nagashima, M., Khan, M. et al. Mutational analysis of p73 and p53 in human cancer cell lines. Oncogene 18, 3415–3421 (1999). https://doi.org/10.1038/sj.onc.1202677
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202677
Keywords
This article is cited by
-
Comparison of clinical and molecular characteristics of patients with acute myeloid leukemia and either TP73 or TP53 mutations
Leukemia (2021)
-
Hyper-O-GlcNAcylation induces cisplatin resistance via regulation of p53 and c-Myc in human lung carcinoma
Scientific Reports (2017)
-
Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade
Scientific Reports (2016)
-
Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21waf1/cip1 among human bronchogenic carcinomas
Molecular Cancer (2005)
-
Effects of inducible overexpression of DNp73α on cancer cell growth and response to treatment in vitro and in vivo
Cell Death & Differentiation (2005)