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P73 expression in basal layers of head and neck squamous epithelium: a role in differentiation and carcinogenesis in concert with p53 and p63?

Oncogene volume 20, pages 5302–5312 (2001)Cite this article

Abstract

P73, a p53-homologue gene, has been studied for its possible role in head and neck squamous epithelium (HNSE) differentiation and carcinogenesis. P73 RNA and protein were analysed in 50 biopsies, including well- and moderately-differentiated carcinomas, and 21 matched normal adjacent tissues. P73 immunohistochemical analyses revealed intense p73 nuclear staining in basal and parabasal cells of normal squamous epithelium, in contrast with complete absence of staining in the more superficial cell layers. Moderately-differentiated carcinomas demonstrated homogeneous and diffuse staining in all tumour cells, while only basal cells were stained in well-differentiated carcinomas as in normal tissue. No correlation was observed between p73 and p53 protein expression. Immunostaining for p63, another p53-related protein previously described as being involved in HNSE morphogenesis and overexpressed in head and neck squamous cell carcinomas (HNSCC), was found to be similar to p73 labelling in carcinomas, but spread to the more differentiated layers in normal epithelium. Biallelic expression of p73 was found in tumours as well as in matched normal tissues. Comparison of p73 transcript levels between tumours and normal tissues showed decreased mRNA expression in 5/17 (30%) tumours independently of the differentiation status. Mutation and loss of heterozygosity analyses of the p73 gene revealed wild type status and no deletion. Our results strongly suggest that: (i) p73 is associated with homeostasis and control of differentiation of head and neck squamous epithelium probably in concert with p53 and p63; (ii) down-regulation of p73 expression could participate in HNSE carcinogenesis.

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References

  • Ahomadegbe JC, Barrois M, Fogel S, LeBihan ML, Douc-Rasy S, Duvillard P, Armand JP, Riou G . 1995 Oncogene 10: 1217–1227

  • Ahomadegbe JC, Tourpin S, Kaghad M, Zelek L, Vayssade M, Mathieu MC, Rochard F, Spielmann M, Tursz T, Caput D, Riou G, Bénard J . 2000 Oncogene 19: 5413–5418

  • Brash DE, Ponten J . 1998 Cancer Survey 32: 69–113

  • Brenner L, Muñoz-Antonia T, Vellucci VF, Zhou ZL, Reiss M . 1993 Cell Growth Differ. 4: 993–1004

  • Cai Y, Yang G, Nie Y, Wang LD, Zhao X, Song YL, Seril D, Liao J, Xing EP, Yang CS . 2000 Carcinogenesis 21: 683–689

  • Casciano I, Ponzoni M, Cunsolo C, Tonini G, Romani M . 1999 Cell Death Differ. 6: 391–393

  • Celli J, Duijf P, Hamel BCJ, Bamshad M, Kramer B, Smits APT, Newbury-Ecob R, Hennekam RCM, Van Buggenhout G, Van Haerigen A, Woods CG, Van Essen AJ, De Waal R, Vriend G, Haber DA, Yang A, McKeon F, Brunner HG, Van Bokhoven H . 1999 Cell 99: 143–153

  • De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M, Melino G . 1998 J. Exp. Med. 188: 1763–1768

  • De Laurenzi V, Catani M, Costanzo A, Terrinoni A, Corazzari M, Levrero M, Knight R, Melino G . 1999 Cell Death Differ. 6: 389–390

  • Dobbelstein M, Wienzek S, König C, Roth J . 1999 Oncogene 18: 2101–2106

  • Hall PA, Campbell SJ, O'Neill M, Royston DJ, Nylander K, Carey FA, Kernohan NM . 2000 Carcinogenesis 21: 153–160

  • Han S, Semba S, Abe T, Makino N, Furukawa T, Fukushige S, Takahashi H, Sakurada A, Sato M, Shiiba K, Matsuno S, Nimura Y, Nakagawara A, Horii A . 1999 Eur. J. Surg. Oncol. 25: 194–198

  • Harris CC, Hollstein M . 1993 New Engl. J. Med. 329: 1318–1327

  • Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidranski D . 2000 Proc. Natl. Acad. Sci. USA 97: 5462–5467

  • 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, Nakagawara A . 1999 Oncogene 18: 1061–1066

  • Jost CA, Marin MC, Kaelin Jr WG . 1997 Nature 389: 191–194

  • Kaelin WG . 1999 J. Natl. Cancer I. 91: 594–598

  • Kaghad M, Bonnet H, Yang A, Creancler L, Biscan JC, Valent A, Minty A, Chalon P, Lellas JM, Dumont X, Ferrara P, McKeon F, Caput D . 1997 Cell 90: 809–819

  • Kang MN, Park BJ, Byun DS, Park JI, Kim HJ, Park JH, Chi SG . 2000 Clin. Cancer Res. 6: 1767–1771

  • Levine AJ . 1994 Brit. J. Cancer 69: 409–416

  • Liefer KM, Koster MI, Wang XJ, Yang A, McKeon F, Roop DR . 2000 Cancer Res. 60: 4016–4020

  • Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI, Liu W . 1998 Cancer Res. 58: 2347–2349

  • Marin MC, Jost CA, Irwin MS, DeCaprio JA, Caput D, Kaelin Jr WG . 1998 Mol. Cell. Biol. 18: 6316–6324

  • Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A . 1999 Nature 398: 708–713

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

  • Pozniak CD, Radinovic S, Yang A, McKeon F, Kaplan DR, Miller FD . 2000 Science 289: 304–306

  • Roth J, König C, Wienzek S, Weigel S, Ristea S, Dobbelstein M . 1998 J. Virol. 72: 8510–8516

  • Rotter V, Aloni-Grinstein R, Schwartz D, Elkind NB, Simons A, Wolkowicz R, Lavigne M, Beserman P, Kapon A, Goldfinger N . 1994 Semin. Cancer Biol. 5: 229–236

  • Senoo M, Seki N, Ohira M, Sugano S, Watanabe M, Tachibana M, Tanaka T, Shinkai Y, Kato H . 1998 Biochem. Biophys. Res. Commun. 248: 603–607

  • Shishikura T, Ichimiya S, Ozaki T, Nimura Y, Kegeyama H, Nakamura Y, Sakiyama S, Miyauchi M, Yamamoto N, Suzuki M, Nakajima N, Nakagawara A . 1999 Int. J. Cancer 84: 321–325

  • Soussi T, Legros Y, Lubin R, Ory K, Schlichtholz B . 1994 Int. J. Cancer 57: 1–9

  • Steegenga WT, Shvarts A, Riteco N, Bos JL, Jochemsen AG . 1999 Mol. Cell. Biol. 19: 3885–3894

  • Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidranski D . 1998 Nat. Med. 4: 747

  • Woodworth CD, Wang H, Simpson S, Alvarez-Salas LM, Notario V . 1993 Cell Growth Differ. 4: 367–376

  • Yamaguchi K, Wu L, Caballero OL, Hibi K, Trink B, Resto V, Cairns P, Okami K, Koch WM, Sidranski D, Jen J . 2000 Int. J. Cancer 86: 684–689

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

  • Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F . 1999 Nature 398: 714–718

  • Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J, Vagner C, Bonnet H, Dikkes P, Sharpe A, McKeon F, Caput D . 2000 Nature 404: 99–103

  • Yokomizo A, Mai M, Tindall DJ, Cheng L, Bostwick DG, Naito S, Smith DI, Liu W . 1999 Oncogene 18: 1629–1633

  • Zaika AI, Kovalev S, Marchenko ND, Moll UM . 1999 Cancer Res. 59: 3257–3263

  • Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin Jr WG, Oren M, Chen J, Lu H . 1999 Mol. Cell. Biol. 19: 3257–3266

  • Zhu J, Jiang J, Zhou W, Chen X . 1998 Cancer Res. 58: 5061–5065

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Acknowledgements

This article is dedicated to Prof Guy Riou, Honorary Head of the Molecular Pharmacology Department of the Institute Gustave Roussy, in acknowledgement of his invaluable scientific and research teaching. We thank Pr Thierry Soussi for helpful criticisms, Sophie Tourpin for technical assistance and Dr Anthony Saul for editing this manuscript. This work was supported by grants from Sanofi-Recherches Labège, Institut Gustave Roussy Villejuif (CRC grant No 98-20), and La Ligue contre le Cancer ‘Comité des Hauts de Seine’ and ‘Comité du Val de Marne’ (France).

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Authors and Affiliations

  1. Département de Biologie Clinique, Unité des Marqueurs Génétiques des Cancers, Institut Gustave Roussy, Villejuif, 94805, France

    Laetitia Faridoni-Laurens, Muriel Vayssade, Marie-Luce Le Bihan, Jean Bénard & Jean-Charles Ahomadegbe

  2. Département d'anatomie pathologique, Institut Gustave Roussy, Villejuif, 94805, France

    Jacques Bosq

  3. Département de Chirurgie Cervico-Faciale, Institut Gustave Roussy, Villejuif, 94805, France

    François Janot

  4. Faculté de Pharmacie, UPJV, 80037, Amiens Cedex, France

    Jean-Charles Ahomadegbe

  5. Sanofi-Recherches, BP 137, 31676, Labège Cedex, France

    Mourad Kaghad & Daniel Caput

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  1. Laetitia Faridoni-Laurens
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Correspondence to Jean-Charles Ahomadegbe.

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Faridoni-Laurens, L., Bosq, J., Janot, F. et al. P73 expression in basal layers of head and neck squamous epithelium: a role in differentiation and carcinogenesis in concert with p53 and p63?. Oncogene 20, 5302–5312 (2001). https://doi.org/10.1038/sj.onc.1204687

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