Abstract
Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. Transcription regulatory regions of MMP genes often contain binding sites for ets transcription factors. We recently isolated a cDNA encoding human E1A-F, a member of the ets oncogene family, and showed that E1A-F can upregulate MMP genes by CAT assay. We attempted to investigate the relationship between E1A-F mRNA expression and MMP protein expression in four different types of oral squamous-cell-carcinoma-derived cell lines (HSC 3, SAS, KB, and Ca 9.22). HSC 3 and SAS are highly invasive cell lines when they are injected in the tongue of nude mice. Raft culture of HSC 3 and SAS revealed the same characteristics as seen in tumors implanted in vivo. Both type I collagenase (MMP-1) and 92-kd type IV collagenase (MMP-9) were detected in cultured HSC 3 and SAS cells. E1A-F mRNA was demonstrated to be highly expressed in HSC 3 and SAS by Northern blotting, and in situ hybridization confirmed E1A-F mRNA expression at the invasion front of tumor cells seeded on collagen gel. On the other hand, KB and Ca 9.22 have little potential for invasion, and MMP-1 and MMP-9 protein and E1A-F mRNA could not be detected. These results suggest that the ets-related E1A-F participates in the regulation of invasion-associated MMP genes and is involved in presenting invasive activity in tumor cells of oral squamous cell carcinoma.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alessandro R., Minafra S., Pucci-Minafra I., Onisto M., Garbisa S., Melchiori A., Tetlow L., Woolley D. E. Metalloproteinase and TIMP expression by the human breast carcinoma cell line 8701-BC. Int J Cancer. 1993 Sep 9;55(2):250–255. doi: 10.1002/ijc.2910550214. [DOI] [PubMed] [Google Scholar]
- Angel P., Baumann I., Stein B., Delius H., Rahmsdorf H. J., Herrlich P. 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region. Mol Cell Biol. 1987 Jun;7(6):2256–2266. doi: 10.1128/mcb.7.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collier I. E., Smith J., Kronberger A., Bauer E. A., Wilhelm S. M., Eisen A. Z., Goldberg G. I. The structure of the human skin fibroblast collagenase gene. J Biol Chem. 1988 Aug 5;263(22):10711–10713. [PubMed] [Google Scholar]
- Gutman A., Wasylyk B. The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J. 1990 Jul;9(7):2241–2246. doi: 10.1002/j.1460-2075.1990.tb07394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higashino F., Yoshida K., Fujinaga Y., Kamio K., Fujinaga K. Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene family. Nucleic Acids Res. 1993 Feb 11;21(3):547–553. doi: 10.1093/nar/21.3.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higashino F., Yoshida K., Noumi T., Seiki M., Fujinaga K. Ets-related protein E1A-F can activate three different matrix metalloproteinase gene promoters. Oncogene. 1995 Apr 6;10(7):1461–1463. [PubMed] [Google Scholar]
- Juarez J., Clayman G., Nakajima M., Tanabe K. K., Saya H., Nicolson G. L., Boyd D. Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. Int J Cancer. 1993 Aug 19;55(1):10–18. doi: 10.1002/ijc.2910550104. [DOI] [PubMed] [Google Scholar]
- Karim F. D., Urness L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. A. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990 Sep;4(9):1451–1453. doi: 10.1101/gad.4.9.1451. [DOI] [PubMed] [Google Scholar]
- Kawahara E., Okada Y., Nakanishi I., Iwata K., Kojima S., Kumagai S., Yamamoto E. The expression of invasive behavior of differentiated squamous carcinoma cell line evaluated by an in vitro invasion model. Jpn J Cancer Res. 1993 Apr;84(4):409–418. doi: 10.1111/j.1349-7006.1993.tb00151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaya M., Yoshida K., Higashino F., Mitaka T., Ishii S., Fujinaga K. A single ets-related transcription factor, E1AF, confers invasive phenotype on human cancer cells. Oncogene. 1996 Jan 18;12(2):221–227. [PubMed] [Google Scholar]
- Kusukawa J., Sasaguri Y., Shima I., Kameyama T., Morimatsu M. Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study. Am J Clin Pathol. 1993 Jan;99(1):18–23. doi: 10.1093/ajcp/99.1.18. [DOI] [PubMed] [Google Scholar]
- Kusukawa J., Sasaguri Y., Shima I., Kameyama T., Morimatsu M. Production of matrix metalloproteinase 2 (gelatinase/type IV collagenase) and 3 (stromelysin) by cultured oral squamous cell carcinoma. J Oral Pathol Med. 1992 May;21(5):221–224. doi: 10.1111/j.1600-0714.1992.tb00105.x. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
- Matrisian L. M., McDonnell S., Miller D. B., Navre M., Seftor E. A., Hendrix M. J. The role of the matrix metalloproteinase stromelysin in the progression of squamous cell carcinomas. Am J Med Sci. 1991 Sep;302(3):157–162. doi: 10.1097/00000441-199109000-00008. [DOI] [PubMed] [Google Scholar]
- Muller D., Wolf C., Abecassis J., Millon R., Engelmann A., Bronner G., Rouyer N., Rio M. C., Eber M., Methlin G. Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res. 1993 Jan 1;53(1):165–169. [PubMed] [Google Scholar]
- Nakajima M., Welch D. R., Belloni P. N., Nicolson G. L. Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res. 1987 Sep 15;47(18):4869–4876. [PubMed] [Google Scholar]
- Nunn M. F., Seeburg P. H., Moscovici C., Duesberg P. H. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature. 1983 Nov 24;306(5941):391–395. doi: 10.1038/306391a0. [DOI] [PubMed] [Google Scholar]
- Okada Y., Tsuchiya H., Shimizu H., Tomita K., Nakanishi I., Sato H., Seiki M., Yamashita K., Hayakawa T. Induction and stimulation of 92-kDa gelatinase/type IV collagenase production in osteosarcoma and fibrosarcoma cell lines by tumor necrosis factor alpha. Biochem Biophys Res Commun. 1990 Sep 14;171(2):610–617. doi: 10.1016/0006-291x(90)91190-4. [DOI] [PubMed] [Google Scholar]
- Powell W. C., Knox J. D., Navre M., Grogan T. M., Kittelson J., Nagle R. B., Bowden G. T. Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. Cancer Res. 1993 Jan 15;53(2):417–422. [PubMed] [Google Scholar]
- Sato H., Seiki M. Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene. 1993 Feb;8(2):395–405. [PubMed] [Google Scholar]
- Shima I., Sasaguri Y., Kusukawa J., Nakano R., Yamana H., Fujita H., Kakegawa T., Morimatsu M. Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer. 1993 Apr;67(4):721–727. doi: 10.1038/bjc.1993.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shindoh M., Sun Q., Pater A., Pater M. M. Prevention of carcinoma in situ of human papillomavirus type 16-immortalized human endocervical cells by retinoic acid in organotypic raft culture. Obstet Gynecol. 1995 May;85(5 Pt 1):721–728. doi: 10.1016/0029-7844(95)00043-q. [DOI] [PubMed] [Google Scholar]
- Wasylyk B., Hahn S. L., Giovane A. The Ets family of transcription factors. Eur J Biochem. 1993 Jan 15;211(1-2):7–18. doi: 10.1007/978-3-642-78757-7_2. [DOI] [PubMed] [Google Scholar]
- Wasylyk C., Gutman A., Nicholson R., Wasylyk B. The c-Ets oncoprotein activates the stromelysin promoter through the same elements as several non-nuclear oncoproteins. EMBO J. 1991 May;10(5):1127–1134. doi: 10.1002/j.1460-2075.1991.tb08053.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wotton D., Ghysdael J., Wang S., Speck N. A., Owen M. J. Cooperative binding of Ets-1 and core binding factor to DNA. Mol Cell Biol. 1994 Jan;14(1):840–850. doi: 10.1128/mcb.14.1.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xin J. H., Cowie A., Lachance P., Hassell J. A. Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. Genes Dev. 1992 Mar;6(3):481–496. doi: 10.1101/gad.6.3.481. [DOI] [PubMed] [Google Scholar]
- Yoshida K., Narita M., Fujinaga K. Binding sites of HeLa cell nuclear proteins on the upstream region of adenovirus type 5 E1A gene. Nucleic Acids Res. 1989 Dec 11;17(23):10015–10034. doi: 10.1093/nar/17.23.10015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zucker S., Lysik R. M., Malik M., Bauer B. A., Caamano J., Klein-Szanto A. J. Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis. Int J Cancer. 1992 Sep 30;52(3):366–371. doi: 10.1002/ijc.2910520307. [DOI] [PubMed] [Google Scholar]
- de Taisne C., Gegonne A., Stehelin D., Bernheim A., Berger R. Chromosomal localization of the human proto-oncogene c-ets. Nature. 1984 Aug 16;310(5978):581–583. doi: 10.1038/310581a0. [DOI] [PubMed] [Google Scholar]



