Abstract
The present study demonstrates alterations in the regulation of matrix metalloproteinase-2 (MMP-2) expression in response to insulin like growth factor-1 (IGF-1) in a H-ras transformed cell line, C3, which is capable of metastasis formation. These changes in MMP-2 expression in response to IGF-1 treatment did not occur in either non-transformed parental 10 T1/2 cells or in H-ras transformed cells (NR3 cells) which are capable of benign tumour formation. IGF-1 treatment of C3 cells resulted in increased expression of MMP-2 gelatinolytic activity and increased expression of MMP-2 mRNA levels. The IGF-1 mediated alterations in MMP-2 mRNA levels were dependent upon de novo protein synthesis and independent of transcriptional events, but dependent upon post-transcriptional regulatory events. Most notably, IGF-1 can regulate MMP-2 mRNA expression in C3 cells through a mechanism involving MMP-2 message stabilization. This study demonstrates aspects of the temporal regulatory mechanisms of MMP-2 expression in response to insulin-like growth factor-1 in a H-ras transformed fibrosarcoma cell line capable of metastasis formation and thereby, provides further insight into the altered growth regulatory program associated with H-ras mediated cellular transformation and malignant progression.
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References
Wright JA, Egan SE, Greenberg AH: Genetic regulation of metastatic progression. Anticancer Res 10: 1247–1256, 1990
Chambers AF, Tuck AB: Ras responsive genes and tumor metastasis. Crit Rev Oncogenesis 4: 95–114, 1993
Chambers AH, Matrisian LM: Changing views of the role of matrix metalloproteinases in metastasis. J Nat Canc Inst 89: 1260–1270, 1997
Witty JP, Wright JH, Matrisian L: Matrix metalloproteinases are expressed during ductal and alveolar mammary morphogenesis, and misregulation of stromelysin-1 in transgenic mice induces unscheduled alveolar development. Mol Biol Cell 16: 1287–1303, 1995
Giambernardi K, Bai G, Kitagawa T, Tsuru D: Overview of matrix metalloproteinase expression in cultured human cells. 16: 483–496, 1998
Vincenti MP, Coon CI, Mengshol JA, Yocum S, Mitchell P, Brinckerhoff CE: Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13) from rabbit synovial fibroblasts: differential expression with collagenase-1 (matrix metalloproteinase-1). Biochem J 331: 341–346, 1998
Nakano A, Tani E, Miyazaki K, Yamamoto Y, Furuyama J: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83: 298–307, 1995
Aho S, Rouda S, Kennedy SH, Qin H, Tan EML: Regulation of human interstitial collagenase (matrix metalloproteinase-1) promoter activity by fibroblast growth factor. Eur J Biochem 247: 503–510, 1997
Rawdanowicz TJ, Hampton AL, Nagase H, Woolley DE, Salamonsen LA: Matrix metalloproteinase production by cultured human endometrial stromal cells: Identification of interstitial collagenase, gelatinase A, gelatinase B, and stromelysin-1, and differential regulation by interleukin-1 and tumor necrosis factor alpha. J Clin Endo Metab 79: 530–536, 1994
Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja L, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase. J Biol Chem 266: 16485–16490, 1991
Overall CM, Wrana J, Sodek J: Transforming growth factor beta regulation of collagenase, 72 kDa progelatinase, TIMP, and PAI-1 expression in rat bone cell populations and human fibroblasts. Conn Tissue Res 20: 289–294, 1989
Samuel SK, Hurta RAR, Kondaiah P, Khalil N, Turley EA, Wright JA, Greenberg AH: Autocrine induction of tumor protease production and invasion by a metallothionein-regulated TGF-beta-1 (Ser 223, 225). EMBO J 11: 1599–1605, 1992
Crawford HC, Matrisian LM: Mechanisms controlling the transcription of matrix metalloproteinase genes in normal and neoplastic cells. Enzyme Prot 49: 20–37, 1996
Corcoran ML, Hewitt RE, Kleiner DE, Stetler-Stevenson WG: MMP-2: Expression, activation and inhibition. Enzyme Prot 49: 7–19, 1996
Long L, Navab R, Brodt P: Regulation of the Mr 72,000 type IV collagenase by the type I insulin like growth factor receptor. Cancer Res 58: 3242–3247, 1998
Hurta RAR, Huang A, Wright JA: Basic fibroblast growth factor selectively regulates ornithine decarboxylase gene expression in malignant H-ras transformed cells. J Cell Biochem 60: 572–583, 1996
Egan SE, McClarty GA, Jarolim L, Wright JA, Spiro I, Hager G, Greenberg AH: Expression of H-ras correlates with metastatic potential: Evidence for direct regulation of the metastatic phenotype in 10 T1/2 and NIH 3T3 cells. Mol Cell Biol 7: 830–837, 1987
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Yoon, A., Hurta, R.A. Insulin like growth factor-1 selectively regulates the expression of matrix metalloproteinase-2 in malignant H-ras transformed cells. Mol Cell Biochem 223, 1–6 (2001). https://doi.org/10.1023/A:1017549222677
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DOI: https://doi.org/10.1023/A:1017549222677