Modulation of Mr 72,000 and Mr 92,000 type-IV collagenase (gelatinase A and B) gene expression by interferons alpha and gamma in human melanoma
✍ Scribed by Erkki S. Hujanen; Anne Väisänen; Aiping Zheng; Karl Trygdvason; Taina Turpeenniemi-Hujanen
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 796 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
The purpose of this study was to determine how interferons a and 4 influence the expression of M, 72,000 type-IV collagenase (gelatinase A) and M, 92,000 type-VI collagenase (gelatinase B) genes and whether there are differences in their gene expression. Special emphasis was focused on the treatment time. Total cellular RNA from A2058 human melanoma cells treated for various time periods with IFN-a or y was analyzed by Northernand slot-blot hybridization. Both M, 72,000 and M, 92,000 type-IV collagenase mRNAs were detectable in A2058 cells and mRNA levels for both gelatinases were significantly upregulated in the cells treated for a short time period with either IFN-a or y. In contrast, a long-term treatment (7 days) with these drugs markedly down-regulated the genes for both gelatinase A and 8. Zymographic analysis showed that human melanoma primarily secretes the gelatinase-A activity, which showed changes similar to those seen in the corresponding mRNA after the treatments with interferons. The expression of gelatinase-B activity was, however, detectable only transiently during the stimulating phase with IFN-a. Western immunoblot analysis showed that alterations in the levels of immunoreactive protein of gelatinase A in the cells correlated with the mRNA levels after the treatments. These findings suggest that IFN-a and I F N y are potent regulators of both M, 72,000 and M, 92,000 type-IV collagenase/gelatinase A and B genes in human melanoma showing biphasic and parallel effects on mRNA levels of both enzymes, depending on the treatment time, and that the M, 72,000 metalloproteinase/gelatinase A is the predominant basement-membrane-degrading type-IV collagenase in human melanoma.