Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jun;80(8):1185–1189. doi: 10.1038/sj.bjc.6690484

Frequent loss of expression or aberrant alternative splicing of P2XM, a p53-inducible gene, in soft-tissue tumours

G Nawa 1,2, Y Miyoshi 1, H Yoshikawa 2,3, T Ochi 2, Y Nakamura 1,4
PMCID: PMC2362367  PMID: 10376970

Abstract

We investigated expression of a human p53-inducible gene, P2XM, a member of the P2X-receptor family of ATP-gated ion channels, in 56 human primary soft-tissue tumours including 47 sarcomas and nine benign tumors. Among the 47 sarcomas examined by reverse transcription polymerase chain reaction, 12 had lost expression of this gene and 22 revealed altered splicing patterns; among the nine benign tumours, four showed no expression of P2XM and three revealed aberrant splicing patterns involving transmembrane domains M1 and/or M2. As the aberrant transcripts lacked either or both of those domains, the protein products probably lacked normal function. We also looked for p53 mutations and mdm2 overexpression in the same panel of tumours and found them in 13 tumours, all but three of which had shown altered expression of P2XM. However, 31 (72%) of the 43 tumours that carried wild-type p53 without mdm2 overexpression had revealed aberrant P2XM expression. Our results suggest that disorder of P2XM expression may play a crucial role in the genesis of benign and malignant tumours in soft tissues, and that one or more genetic factors other than p53 or mdm2 contribute significantly to aberrant P2XM expression. © 1999 Cancer Research Campaign

Keywords: P2XM, alternative splice, soft tissue sarcoma, p53, mdm2

Full Text

The Full Text of this article is available as a PDF (102.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreassen A., Oyjord T., Hovig E., Holm R., Flørenes V. A., Nesland J. M., Myklebost O., Høie J., Bruland O. S., Børresen A. L. p53 abnormalities in different subtypes of human sarcomas. Cancer Res. 1993 Feb 1;53(3):468–471. [PubMed] [Google Scholar]
  2. Buckbinder L., Talbott R., Velasco-Miguel S., Takenaka I., Faha B., Seizinger B. R., Kley N. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995 Oct 19;377(6550):646–649. doi: 10.1038/377646a0. [DOI] [PubMed] [Google Scholar]
  3. Castresana J. S., Barrios C., Gómez L., Kreicbergs A. No association between c-myc amplification and TP53 mutation in sarcoma tumorigenesis. Cancer Genet Cytogenet. 1994 Aug;76(1):47–49. doi: 10.1016/0165-4608(94)90070-1. [DOI] [PubMed] [Google Scholar]
  4. Castresana J. S., Rubio M. P., Gómez L., Kreicbergs A., Zetterberg A., Barrios C. Detection of TP53 gene mutations in human sarcomas. Eur J Cancer. 1995;31A(5):735–738. doi: 10.1016/0959-8049(95)00121-x. [DOI] [PubMed] [Google Scholar]
  5. Cordon-Cardo C., Latres E., Drobnjak M., Oliva M. R., Pollack D., Woodruff J. M., Marechal V., Chen J., Brennan M. F., Levine A. J. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res. 1994 Feb 1;54(3):794–799. [PubMed] [Google Scholar]
  6. Enjoji M., Hashimoto H. Diagnosis of soft tissue sarcomas. Pathol Res Pract. 1984 Jan;178(3):215–226. doi: 10.1016/S0344-0338(84)80102-8. [DOI] [PubMed] [Google Scholar]
  7. Felix C. A., Kappel C. C., Mitsudomi T., Nau M. M., Tsokos M., Crouch G. D., Nisen P. D., Winick N. J., Helman L. J. Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma. Cancer Res. 1992 Apr 15;52(8):2243–2247. [PubMed] [Google Scholar]
  8. Furuhata T., Tokino T., Urano T., Nakamura Y. Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity. Oncogene. 1996 Nov 7;13(9):1965–1970. [PubMed] [Google Scholar]
  9. Haupt Y., Maya R., Kazaz A., Oren M. Mdm2 promotes the rapid degradation of p53. Nature. 1997 May 15;387(6630):296–299. doi: 10.1038/387296a0. [DOI] [PubMed] [Google Scholar]
  10. Kastan M. B., Zhan Q., el-Deiry W. S., Carrier F., Jacks T., Walsh W. V., Plunkett B. S., Vogelstein B., Fornace A. J., Jr A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–597. doi: 10.1016/0092-8674(92)90593-2. [DOI] [PubMed] [Google Scholar]
  11. Kubbutat M. H., Jones S. N., Vousden K. H. Regulation of p53 stability by Mdm2. Nature. 1997 May 15;387(6630):299–303. doi: 10.1038/387299a0. [DOI] [PubMed] [Google Scholar]
  12. Latres E., Drobnjak M., Pollack D., Oliva M. R., Ramos M., Karpeh M., Woodruff J. M., Cordon-Cardo C. Chromosome 17 abnormalities and TP53 mutations in adult soft tissue sarcomas. Am J Pathol. 1994 Aug;145(2):345–355. [PMC free article] [PubMed] [Google Scholar]
  13. Leach F. S., Tokino T., Meltzer P., Burrell M., Oliner J. D., Smith S., Hill D. E., Sidransky D., Kinzler K. W., Vogelstein B. p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 1993 May 15;53(10 Suppl):2231–2234. [PubMed] [Google Scholar]
  14. Masuda H., Miller C., Koeffler H. P., Battifora H., Cline M. J. Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7716–7719. doi: 10.1073/pnas.84.21.7716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miyashita T., Reed J. C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 Jan 27;80(2):293–299. doi: 10.1016/0092-8674(95)90412-3. [DOI] [PubMed] [Google Scholar]
  16. Morris G. F., Bischoff J. R., Mathews M. B. Transcriptional activation of the human proliferating-cell nuclear antigen promoter by p53. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):895–899. doi: 10.1073/pnas.93.2.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Okamoto K., Beach D. Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J. 1994 Oct 17;13(20):4816–4822. doi: 10.1002/j.1460-2075.1994.tb06807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oliner J. D., Kinzler K. W., Meltzer P. S., George D. L., Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992 Jul 2;358(6381):80–83. doi: 10.1038/358080a0. [DOI] [PubMed] [Google Scholar]
  19. Owens G. P., Hahn W. E., Cohen J. J. Identification of mRNAs associated with programmed cell death in immature thymocytes. Mol Cell Biol. 1991 Aug;11(8):4177–4188. doi: 10.1128/mcb.11.8.4177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schneider-Stock R., Radig K., Oda Y., Mellin W., Rys J., Niezabitowski A., Roessner A. p53 gene mutations in soft-tissue sarcomas--correlations with p53 immunohistochemistry and DNA ploidy. J Cancer Res Clin Oncol. 1997;123(4):211–218. doi: 10.1007/BF01240317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stratton M. R., Moss S., Warren W., Patterson H., Clark J., Fisher C., Fletcher C. D., Ball A., Thomas M., Gusterson B. A. Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene. Oncogene. 1990 Sep;5(9):1297–1301. [PubMed] [Google Scholar]
  22. Taubert H., Meye A., Würl P. Prognosis is correlated with p53 mutation type for soft tissue sarcoma patients. Cancer Res. 1996 Sep 15;56(18):4134–4136. [PubMed] [Google Scholar]
  23. Taubert H., Würl P., Meye A., Berger D., Thamm B., Neumann K., Hinze R., Schmidt H., Rath F. W. Molecular and immunohistochemical p53 status in liposarcoma and malignant fibrous histiocytoma: identification of seven new mutations for soft tissue sarcomas. Cancer. 1995 Oct 1;76(7):1187–1196. doi: 10.1002/1097-0142(19951001)76:7<1187::aid-cncr2820760714>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  24. Toguchida J., Yamaguchi T., Ritchie B., Beauchamp R. L., Dayton S. H., Herrera G. E., Yamamuro T., Kotoura Y., Sasaki M. S., Little J. B. Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res. 1992 Nov 15;52(22):6194–6199. [PubMed] [Google Scholar]
  25. Urano T., Nishimori H., Han H., Furuhata T., Kimura Y., Nakamura Y., Tokino T. Cloning of P2XM, a novel human P2X receptor gene regulated by p53. Cancer Res. 1997 Aug 1;57(15):3281–3287. [PubMed] [Google Scholar]
  26. Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. doi: 10.1016/0092-8674(92)90421-8. [DOI] [PubMed] [Google Scholar]
  27. Wu X., Bayle J. H., Olson D., Levine A. J. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993 Jul;7(7A):1126–1132. doi: 10.1101/gad.7.7a.1126. [DOI] [PubMed] [Google Scholar]
  28. Würl P., Taubert H., Bache M., Kroll J., Meye A., Berger D., Siermann A., Holzhausen H. J., Hinze R., Schmidt H. Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors. Int J Cancer. 1996 Aug 22;69(4):317–323. doi: 10.1002/(SICI)1097-0215(19960822)69:4<317::AID-IJC14>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  29. el-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M., Lin D., Mercer W. E., Kinzler K. W., Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. doi: 10.1016/0092-8674(93)90500-p. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES