Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells

Nishi,Hirotaka; Kuroda,Masahiko; Isaka,Keiichi

doi:10.3892/or.2013.2527

Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells

Authors:
- Hirotaka Nishi
- Masahiko Kuroda
- Keiichi Isaka
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan, Department of Molecular Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
Published online on: June 7, 2013 https://doi.org/10.3892/or.2013.2527
Pages: 751-756

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The human matrix metalloproteinase (MMP)-26, also called matrilysin-2 or endometase, has been isolated as a matrilysin (MMP-7) homolog. Several reports describe that MMP-26 may be related to the development of endometrial carcinomas. Total RNAs were isolated from 51 normal endometrial tissue samples, 6 endometrial hyperplasia tissue samples and 30 endometrial carcinomas. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate MMP-26 mRNA expression levels. We examined the effect of estrogen and its receptor (ER) on MMP-26 expression in endometrial carcinoma cell lines by real-time RT-PCR, western blot analysis and luciferase assays. To examine protein-DNA binding between ER and MMP-26 promoter, we performed chromatin immunoprecipitation (ChIP) assay. Real-time RT-PCR analysis revealed that MMP-26 mRNA expression was significantly higher in the normal human endometria and hyperplasias compared with that in endometrial carcinomas. Estrogen not only transactivated the MMP-26 promoter activity but also enhanced endogenous MMP-26 expression. The MMP-26 promoter region contains a putative ER response element (ERE). Nuclear ER protein interacted with ERE on the MMP-26 promoter by ChIP assay. We found a significant difference in MMP-26 expression in normal and malignant endometrial tissue samples and that estrogen induced MMP-26 expression. Estrogen may induce endometrial hyperplasia but not endometrial carcinoma. Our results provide evidence that regulation of MMP-26 promoter activity by estrogen may represent a mechanism for endometrial carcinogenesis.

View Figures

View References

1	Nagase H and Woessner JF Jr: Matrix metalloproteinases. J Biol Chem. 274:21491–21494. 1999. View Article : Google Scholar
2	Pilka R, Norata GD, Domanski H, Andersson C, Hansson S, Eriksson P and Casslen B: Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer. Gynecol Oncol. 94:661–670. 2004. View Article : Google Scholar
3	Park HI, Ni J, Gerkema FE, Liu D, Belozerov VE and Sang QX: Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor. J Biol Chem. 275:20540–20544. 2000. View Article : Google Scholar : PubMed/NCBI
4	Stetler-Stevenson WG, Aznavoorian S and Liotta LA: Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 9:541–573. 1993. View Article : Google Scholar : PubMed/NCBI
5	Murray GI, Duncan ME, O’Neil P, Melvin WT and Fothergill JE: Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med. 2:461–462. 1996. View Article : Google Scholar : PubMed/NCBI
6	Nelson AR, Fingleton B, Rothenberg ML and Matrisian LM: Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 18:1135–1149. 2000.PubMed/NCBI
7	Chambers AF and Matrisian LM: Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 89:1260–1270. 1997. View Article : Google Scholar : PubMed/NCBI
8	Sternlicht MD, Lochter A, Sympson CJ, et al: The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell. 98:137–146. 1999. View Article : Google Scholar : PubMed/NCBI
9	Velasco G, Pendas AM, Fueyo A, Knauper V, Murphy G and Lopez-Otin C: Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem. 274:4570–4576. 1999. View Article : Google Scholar
10	de Coignac AB, Elson G, Delneste Y, et al: Cloning of MMP-26. A novel matrilysin-like proteinase. Eur J Biochem. 267:3323–3329. 2000.PubMed/NCBI
11	Marchenko GN, Ratnikov BI, Rozanov DV, Godzik A, Deryugina EI and Strongin AY: Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin. Biochem J. 356:705–718. 2001. View Article : Google Scholar : PubMed/NCBI
12	Uria JA and Lopez-Otin C: Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res. 60:4745–4751. 2000.
13	Trabert B, Wentzensen N, Yang HP, Sherman ME, Hollenbeck AR, Park Y and Brinton LA: Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk? Int J Cancer. 132:417–426. 2013. View Article : Google Scholar : PubMed/NCBI
14	Isaka K, Nishi H, Nakai H, Nakada T, Feng Li Y, Ebihara Y and Takayama M: Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma. Cancer. 97:79–89. 2003. View Article : Google Scholar : PubMed/NCBI
15	Cooke PS, Buchanan DL, Young P, et al: Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci USA. 94:6535–6540. 1997. View Article : Google Scholar : PubMed/NCBI
16	Pierro E, Minici F, Alesiani O, et al: Stromal-epithelial interactions modulate estrogen responsiveness in normal human endometrium. Biol Reprod. 64:831–838. 2001. View Article : Google Scholar : PubMed/NCBI
17	Li W, Savinov AY, Rozanov DV, et al: Title: Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets α1-antitrypsin serpin. Cancer Res. 64:8657–8665. 2004.PubMed/NCBI
18	Isaka K, Nishi H, Sagawa Y, et al: Establishment of a new human cell line (EN) with TP53 mutation derived from endometrial carcinoma. Cancer Genet Cytogenet. 141:20–25. 2003. View Article : Google Scholar : PubMed/NCBI
19	Nishida M: The Ishikawa cells from birth to the present. Hum Cell. 15:104–117. 2002. View Article : Google Scholar : PubMed/NCBI
20	Mak HY and Parker MG: Use of suppressor mutants to probe the function of estrogen receptor-p160 coactivator interactions. Mol Cell Biol. 21:4379–4390. 2001. View Article : Google Scholar : PubMed/NCBI
21	Banno K, Kisu I, Yanokura M, et al: Progestin therapy for endometrial cancer: the potential of fourth-generation progestin (Review). Int J Oncol. 40:1755–1762. 2012.PubMed/NCBI
22	Xiong Y, Dowdy SC, Eberhardt NL, Podratz KC and Jiang SW: hMLH1 promoter methylation and silencing in primary endometrial cancers are associated with specific alterations in MBDs occupancy and histone modifications. Gynecol Oncol. 103:321–328. 2006. View Article : Google Scholar : PubMed/NCBI
23	Tashiro H, Blazes MS, Wu R, et al: Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 57:3935–3940. 1997.PubMed/NCBI
24	Lax SF, Kendall B, Tashiro H, Slebos RJ and Hedrick L: The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 88:814–824. 2000. View Article : Google Scholar
25	Kawaguchi M, Banno K, Yanokura M, et al: Analysis of candidate target genes for mononucleotide repeat mutation in microsatellite instability-high (MSI-H) endometrial cancer. Int J Oncol. 35:977–982. 2009.PubMed/NCBI
26	Suprun HZ, Taendler-Stolero R, Schwartz J and Ettinger M: Experience with Endopap endometrial sampling in the cytodiagnosis of endometrial carcinoma and its precursor lesions. I A correlative cytologic-histologic-hysteroscopic diagnostic pilot study. Acta Cytol. 38:319–323. 1994.
27	Foulks MJ: The Papanicolaou smear: its impact on the promotion of women’s health. J Obstet Gynecol Neonatal Nurs. 27:367–373. 1998.