Premium
Modulation of M r 72,000 and M r 92,000 type‐IV collagenase (gelatinase A and B) gene expression by interferons alpha and gamma in human melanoma
Author(s) -
Hujanen Erkki S.,
Väisänen Anne,
Zheng Aiping,
Trygdvason Karl,
TurpeenniemiHujanen Taina
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580422
Subject(s) - gelatinase , collagenase , gelatinase a , northern blot , microbiology and biotechnology , gene expression , interstitial collagenase , biology , alpha (finance) , messenger rna , interferon gamma , fibroblast activation protein, alpha , gene , cytokine , enzyme , immunology , biochemistry , medicine , nursing , cancer , patient satisfaction , construct validity , genetics
Abstract The purpose of this study was to determine how interferons α and γ influence the expression of M r 72,000 type‐IV collagenase (gelatinase A) and M r 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‐α or γ was analyzed by Northern‐and slot‐blot hybridization. Both M r 72,000 and M r 92,000 type‐IV collagenase mRNAs were detectable in A2058 cells and mRNA levels for both gelatinases were significantly up‐regulated in the cells treated for a short time period with either IFN‐α or γ. In contrast, a long‐term treatment (7 days) with these drugs markedly down‐regulated the genes for both gelatinase A and B. 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‐α. 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‐α and IFN‐γ are potent regulators of both M r 72,000 and M r 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 r 72,000 metalloproteinase/gelatinase A is the predominant basement‐membrane‐degrading type‐IV collagenase in human melanoma.