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Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes.
Carcinogenesis. 2000 Jun; 21(6):1079-85.C

Abstract

Hepatocyte growth factor (HGF) is thought to play a role in cell motility and invasion. Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. We have previously reported that the Ets-oncogene family transcription factor E1AF positively regulates transcription of MMP genes in transient expression assays and that overexpression of the E1AF gene confers an invasive phenotype on breast cancer cells. Here we examined the effect of HGF on E1AF and MMP gene expression in terms of the invasive potential of the oral squamous cell carcinoma cell line HSC3. HGF stimulated expression of the E1AF gene. The levels of MMP-1, -3 and -9 mRNAs increased in cells treated with HGF and correlated with E1AF upregulation. In contrast, no obvious upregulation of MMP-1 and -9 mRNA was observed in ASE1AFHSC3 cells transfected with the antisense E1AF expression vector into parental HSC3 cells. The wild-type MMP-9 gene promoter was activated by endogenous E1AF in HSC3 cells, and chloramphenicol acetyltransferase (CAT) activities increased when HGF was added to transfected cells. On the other hand, CAT activity was reduced to almost two-thirds of the wild-type activity when HSC3 cells were transfected with a CAT reporter plasmid driven by a mutant MMP-9 promoter lacking the Ets-binding site, and induction of CAT activity was not observed upon addition of HGF. Analysis of organotypic raft cultures revealed that HSC3 cells invaded and degraded collagen gel actively upon addition of HGF. These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion.

Authors+Show Affiliations

Department of Dental Radiology, Hokkaido University School of Dentistry, North 13 West 7 Kita-ku, Sapporo 060-0813, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10836994

Citation

Hanzawa, M, et al. "Hepatocyte Growth Factor Upregulates E1AF That Induces Oral Squamous Cell Carcinoma Cell Invasion By Activating Matrix Metalloproteinase Genes." Carcinogenesis, vol. 21, no. 6, 2000, pp. 1079-85.
Hanzawa M, Shindoh M, Higashino F, et al. Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes. Carcinogenesis. 2000;21(6):1079-85.
Hanzawa, M., Shindoh, M., Higashino, F., Yasuda, M., Inoue, N., Hida, K., Ono, M., Kohgo, T., Nakamura, M., Notani, K., Fukuda, H., Totsuka, Y., Yoshida, K., & Fujinaga, K. (2000). Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes. Carcinogenesis, 21(6), 1079-85.
Hanzawa M, et al. Hepatocyte Growth Factor Upregulates E1AF That Induces Oral Squamous Cell Carcinoma Cell Invasion By Activating Matrix Metalloproteinase Genes. Carcinogenesis. 2000;21(6):1079-85. PubMed PMID: 10836994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes. AU - Hanzawa,M, AU - Shindoh,M, AU - Higashino,F, AU - Yasuda,M, AU - Inoue,N, AU - Hida,K, AU - Ono,M, AU - Kohgo,T, AU - Nakamura,M, AU - Notani,K, AU - Fukuda,H, AU - Totsuka,Y, AU - Yoshida,K, AU - Fujinaga,K, PY - 2000/6/3/pubmed PY - 2000/8/6/medline PY - 2000/6/3/entrez SP - 1079 EP - 85 JF - Carcinogenesis JO - Carcinogenesis VL - 21 IS - 6 N2 - Hepatocyte growth factor (HGF) is thought to play a role in cell motility and invasion. Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. We have previously reported that the Ets-oncogene family transcription factor E1AF positively regulates transcription of MMP genes in transient expression assays and that overexpression of the E1AF gene confers an invasive phenotype on breast cancer cells. Here we examined the effect of HGF on E1AF and MMP gene expression in terms of the invasive potential of the oral squamous cell carcinoma cell line HSC3. HGF stimulated expression of the E1AF gene. The levels of MMP-1, -3 and -9 mRNAs increased in cells treated with HGF and correlated with E1AF upregulation. In contrast, no obvious upregulation of MMP-1 and -9 mRNA was observed in ASE1AFHSC3 cells transfected with the antisense E1AF expression vector into parental HSC3 cells. The wild-type MMP-9 gene promoter was activated by endogenous E1AF in HSC3 cells, and chloramphenicol acetyltransferase (CAT) activities increased when HGF was added to transfected cells. On the other hand, CAT activity was reduced to almost two-thirds of the wild-type activity when HSC3 cells were transfected with a CAT reporter plasmid driven by a mutant MMP-9 promoter lacking the Ets-binding site, and induction of CAT activity was not observed upon addition of HGF. Analysis of organotypic raft cultures revealed that HSC3 cells invaded and degraded collagen gel actively upon addition of HGF. These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/10836994/Hepatocyte_growth_factor_upregulates_E1AF_that_induces_oral_squamous_cell_carcinoma_cell_invasion_by_activating_matrix_metalloproteinase_genes_ L2 - http://www.diseaseinfosearch.org/result/1077 DB - PRIME DP - Unbound Medicine ER -