Abstract
p73 is a novel gene that has high sequence homology and similar gene structure to the tumor suppressor gene p53. We analysed p73 in seven ovarian carcinoma cell lines and a total of 63 human borderline and invasive ovarian tumor samples. Loss of heterozygosity at this locus was observed in 50% of invasive tumors but in none of the borderline tumors. Biallelic expression of the gene was observed in the heterozygous tumor tissues. Direct sequencing and single-strand conformation polymorphism analyses of the p73 cDNA sequence homologous to the highly mutatable region of p53 did not reveal any mutations. When compared to the primary cultures of normal human ovarian surface epithelial cells and immortalized cell lines, four of the seven ovarian carcinoma cell lines, 71% of the invasive tumors, and 92% of the borderline tumor tissues express elevated levels of p73 transcript. Except for the OVCA3 cell line, Western blot analysis of the nuclear extracts prepared from the cell lines showed concordant levels of p73 protein. Our analysis also demonstrated the expression of a spliced variant of p73 transcript with the omission of exon 2 solely in the cancer cell lines and invasive tumor tissues. This exon 2-spliced transcript would give rise to a truncated p73 protein without the N-terminal transactivation domain. In reminiscence of the dominant negative phenotype of the N-terminal truncated variants of another p53-related gene, p63, the expression of the truncated p73 variant form in ovarian tumors may play an important role in the pathogenesis of ovarian 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
References
Chi SW, Ayed A and Arrowsmith CH . 1999 EMBO J 18: 4438–4445
Coles C, Condie A, Chetty U, Steel CM, Evans HJ and Prosser J . 1992 Cancer Res 52: 5291–5298
Davison TS, Vagner C, Kaghad M, Ayed A, Caput D and Arrowsmith CH . 1999 J Biol Chem 274: 18709–18714
Dobbelstein M, Wienzek S, Konig C and Roth J . 1999 Oncogene 18: 2101–2106
Fajac A, Benard J, Lhomme C, Rey A, Duvillard P, Rochard F, Bernaudin JF and Riou G . 1995 Int J Cancer 64: 146–151
Frankel RH, Bayona W, Koslow M and Newcomb EW . 1992 Cancer Res 52: 1427–1433
Hagiwara K, McMenamin MG, Miura K and Harris CC . 1999 Cancer Res 59: 4165–4169
Higashino F, Pipas JM and Shenk T . 1998 Proc Natl Acad Sci USA 95: 15683–15687
Jost CA, Marin MC and Kaelin Jr WG . 1997 Nature 389: 191–194
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
Kovalev S, Marchenko N, Swendeman S, LaQuaglia M and Moll UM . 1998 Cell Growth Differ 9: 897–903
Kubbutat MH, Jones SN and Vousden KH . 1997 Nature 387: 299–303
Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI and Liu W . 1998 Cancer Res 58: 2347–2349
Marin MC, Jost CA, Irwin MS, DeCaprio JA, Caput D and Kaelin Jr WG . 1998 Mol Cell Biol 18: 6316–6324
Mok SC, Bell DA, Knapp RC, Fishbaugh PM, Welch WR, Muto MG, Berkowitz RS and Tsao SW . 1993 Cancer Res 53: 1489–1492
Mok SC, Kwok TT, Berkowitz RS, Barrett AJ and Tsui FWL . 1995 Gyn Oncol 57: 299–303
Nomoto S, Haruki N, Kondo M, Konishi H, Takahashi T, Takahashi T and Takahashi T . 1998 Cancer Res 58: 1380–1383
Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M and Ikawa S . 1998 Nat Med 4: 839–843
Pejovic T . 1995 Ann Med 27: 73–78
Schmale H and Bamberger C . 1997 Oncogene 15: 1363–1367
Shimada A, Kato S, Enjo K, Osada M, Ikawa Y, Kohno K, Obinata M, Kanamaru R and Ishioka C . 1999 Cancer Res 59: 2781–2786
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
Thompson FH, Taetle R, Trent JM, Liu Y, Massey-Brown K, Scott KM, Weinstein RS, Emerson JC, Alberts DS and Nelson MA . 1997 Cancer Genet Cytogenet 96: 106–110
Thut CJ, Goodrich JA and Tjian R . 1997 Genes Dev 11: 1974–1986
Trink B, Okami K, Wu L, Sriuranpong V, Jen J and Sidransky D . 1998 Nat Med 4: 747–748
Wertheim I, Muto MG, Welch WR, Bell DA, Berkowitz RS and Mok SC . 1994 J Natl Cancer Inst 86: 1549–1551
Yaginuma Y and Westphal H . 1992 Cancer Res 52: 4196–4199
Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Doetsch V, Andrews NC, Caput D and McKeon F . 1998 Mol Cell 2: 305–316
Yokomizo A, Mai M, Tindall DJ, Cheng L, Bostwick DG, Naito S, Smith DI and Liu W . 1999 Oncogene 18: 1625–1629
Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin Jr WG, Oren M, Chen J and Lu H . 1999 Mol Cell Biol 19: 3257–3266
Acknowledgements
We acknowledge the provision of p73 antibody from Dr Frank McKeon. This work was supported in part by NIH grants CA70216 (to S-W Ng) and R01CA69453, R01CA69291 and R01CA63381 (to SC Mok).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ng, SW., Yiu, G., Liu, Y. et al. Analysis of p73 in human borderline and invasive ovarian tumor. Oncogene 19, 1885–1890 (2000). https://doi.org/10.1038/sj.onc.1203512
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203512
Keywords
This article is cited by
-
Requirement for TP73 and genetic alterations originating from its intragenic super-enhancer in adult T-cell leukemia
Leukemia (2022)
-
N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy
Oncogene (2013)
-
Association of the p73 gene G4C14-to-A4T14 polymorphism with increased gastric cancer risk in a northwestern Chinese population
Chinese Journal of Clinical Oncology (2008)
-
The role of p73 in hematological malignancies
Leukemia (2006)
-
Prognostic value of increase in transcript levels of Tp73 ΔEx2-3 isoforms in low-grade glioma patients
British Journal of Cancer (2006)