Cell-type specific regulation of human interstitial collagenase-1 gene expression by interleukin-1β (IL-1β) in human fibroblasts and BC-8701 breast cancer cells

Abstract

Interleukin-1 beta (IL-1 beta) is a potent cytokine that stimulates interstitial collagenase-1 (matrix metalloproteinase-1; MMP-1). In this study, we compared the mechanism(s) by which IL-1 beta induces collagenase gene expression in two very different cells, normal human foreskin fibroblasts (HFFs) and an aggressive breast cancer cell line, BC-8701 cells. Northern analysis showed that the time course of collagenase induction was distinct in the two cells: although both cells expressed low levels of MMP-1 constitutively, addition of IL-1 beta increased MMP-1 mRNA in HFFs by 1 h and levels remained high over a 24-h period. In contrast, MMP-1 levels in IL-1 beta-treated BC-8701 cells did not increase until 4 h, peaked by 12 h and then declined. To analyze the transcriptional response, we cloned and sequenced more than 4,300 bp of the human MMP-1 promoter, and from this promoter clone, we prepared a series of 5'-deletion constructs linked to the luciferase reporter and transiently transfected these constructs into both cell types to measure both basal and IL-1 beta induced transcription. When both cell types were uninduced, promoter fragments containing less than 2,900 bp gave only a minimal transcriptional response, while larger fragments showed increased transcriptional activity. With IL-1 beta treatment, significant responsiveness (P < 0.001) in HFFs was seen only with the larger fragments, while in the BC-8701 cells, all fragments were significantly induced with IL-1 beta. Finally, we found that IL-1 beta stabilized MMP-1 mRNA in normal fibroblasts, but not in BC-8701 breast cancer cells. We conclude that both the transcriptional and post-transcriptional regulation of MMP-1 gene expression by IL-1 beta is controlled by cell-type specific mechanisms, and we suggest that IL-1 induced MMP-1 expression in tumor cells and in neighboring stromal cells may amplify the invasive ability of tumor cells.

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

“…MMP-1 mRNA levels from untreated cells decreased by 40% after 3 h of DRB treatment (Fig. 8), similar to reports using other cells (35). MMP-1 mRNA levels from NHKs cultured in media containing atRA or both atRA ϩ TCDD did not decrease during the time points tested.…”

Epstein‐Barr virus latent membrane protein 1 induces the matrix metalloproteinase‐1 promoter via an Ets binding site formed by a single nucleotide polymorphism: Enhanced susceptibility to nasopharyngeal carcinoma

“…24,46 Moreover, in tumor-cell lines, the frequency of homozygotes for 2G was significantly higher than in general populations. Other reports have shown the correlation between the 2G allele and cancer risk in lung cancer, colorectal cancer, melanoma and endometrial cancer.…”

“…The question remains, however, which factors contribute to the cleavage of the latent form of MMP1. According to past studies, 46,52,53 certain melanoma cell lines could not convert the latent form of MMP1 to an active form by themselves. The conclusion was that an active form of MMP3 and serine proteinases produced by normal fibroblasts enhance cleavage of a latent form of MMP1.…”

Interaction between the Elastin Peptide VGVAPG and Human Elastin Binding Protein

“…Expression Plasmids-The Ϫ512ColA-luc plasmid encoding luciferase under the control of the MMP-1 promoter was generated by cloning the 5Ј upstream sequence of MMP-1 into the pGL3Basic reporter plasmid (Promega, Lyon, France), as described previously (26). The cDNA of human EBP cloned in a eukaryotic expression vector (pSC/rSV-EBP) was supplied by Dr. Aleksander Hinek (Hospital for Sick Children, Toronto, Canada).…”