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Adenoviral delivery of p53 gene suppresses expression of collagenase-3 (MMP-13) in squamous carcinoma cells

Oncogene volume 21, pages 1187–1195 (2002)Cite this article

Abstract

Squamous cell carcinomas (SCCs) of the head and neck are characterized by high tendency to invade locally and metastasize to lymph nodes. SCC cells express several matrix metalloproteinases (MMPs) and they often harbor mutations in p53 tumor suppressor gene. Collagenase-3 (MMP-13) is specifically expressed by tumor cells of SCCs and it apparently plays an important role in their invasion and metastasis. We used adenoviral gene delivery to examine the effect of wild-type p53 on MMP-13 expression in four head and neck SCC cell lines with mutated p53. Adenoviral delivery of p53 resulted in potent inhibition in production of proMMP-13 (by 71 to 92%) and collagenase-1 (MMP-1) (by 27 to 93%) by all cell lines in 24 h, whereas production of gelatinase-A (MMP-2) and gelatinase-B (MMP-9) was not altered. Adenoviral expression of p53 also suppressed invasion of SCC cells through Matrigel by 35%. Expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1 was induced 24 h after p53 gene delivery in all SCC cell lines, except one, which lacked detectable p21Waf1/Cip1 expression. Number of viable cells was not altered and no apoptotic cells were seen 24 h after p53 delivery. These results show, that wild-type p53 potently inhibits expression of MMP-13 and MMP-1 by SCC cells independently of its pro-apoptotic effect. Together there results indicate, that p53 exerts a bi-phasic tumor suppressor effect on SCC cells: inhibition of cell invasion followed by induction of programmed cell death.

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Acknowledgements

We thank Ms Johanna Forsten, Ms Hanna Haavisto, Ms Marjo Hakkarainen, Ms Sari Pitkänen and Ms Marita Potila for skillful technical assistance. This study was supported by grants from the Academy of Finland, Sigrid Jusélius Foundation, the Cancer Foundation of Finland, and Turku University Central Hospital, and by research contract with Finnish Life and Pension Insurance Companies. R Ala-aho is a student in Turku Graduate School of Biomedical Sciences.

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Authors and Affiliations

  1. Centre for Biotechnology, University of Turku and Åbo Akademi University, FIN-20520, Turku, Finland

    Risto Ala-aho & Veli-Matti Kähäri

  2. Department of Medical Biochemistry, University of Turku, FIN-20520, Turku, Finland

    Risto Ala-aho & Veli-Matti Kähäri

  3. Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Central Hospital, FIN-20520, Turku, Finland

    Reidar Grénman

  4. University Research, Des Moines University, Des Moines, 50312, Iowa, IA, USA

    Prem Seth

  5. Department of Dermatology, University of Turku, FIN-20520, Turku, Finland

    Veli-Matti Kähäri

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  1. Risto Ala-aho
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Correspondence to Veli-Matti Kähäri.

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Ala-aho, R., Grénman, R., Seth, P. et al. Adenoviral delivery of p53 gene suppresses expression of collagenase-3 (MMP-13) in squamous carcinoma cells. Oncogene 21, 1187–1195 (2002). https://doi.org/10.1038/sj.onc.1205198

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