Cell Growth & Differentiation, Vol 8, Issue 2 243-250, Copyright © 1997 by American Association of Cancer Research

ARTICLES

Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth factor beta

N Johansson, J Westermarck, S Leppa, L Hakkinen, L Koivisto, C Lopez-Otin, J Peltonen, J Heino and VM Kahari
Department of Dermatology, Turku University Central Hospital, Finland.

Collagenase-3 (matrix metalloproteinase 13; MMP-13) is a novel matrix metalloproteinase, the expression of which to date has only been detected in human breast carcinoma tissue and osteoarthritic cartilage. Here, we show that MMP-13 transcripts are expressed by human HaCaT keratinocytes but not by primary human epidermal keratinocytes. The levels of MMP-13 mRNAs in HaCaT cells were enhanced up to 130- and 45-fold by tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), respectively. The maximal induction of MMP-13 mRNAs by TNF-alpha was noted after a 6-h incubation, whereas with TGF-beta, the maximal stimulation was observed after 24 h. The up-regulation of MMP-13 mRNA abundance by TNF-alpha and TGF-beta was dependent on protein synthesis and was prevented partially by dexamethasone and retinoic acid. Nuclear run-on assays demonstrated activation of MMP-13 gene transcription by TNF-alpha maximally at the 2-h time point and by TGF-beta after 12 h of treatment. Incubation of HaCaT keratinocytes with TNF-alpha and TGF-beta also increased production of proMMP-13 into the culture media, as detected by Western blotting. Our data indicate that the MMP-13 gene is expressed by transformed epidermal keratinocytes, suggesting a role for MMP-13 in the invasive capacity of human epidermal malignancies.

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