| Endometrial carcinoma is a malignancy that occurs in endometrial epithelial cells,and its global incidence has increased. Estrogen plays an important role inmaintaining the female phenotype and the normal menstrual cycle while it can alsohave adverse effects, especially promotion of estrogen-dependent tumors. It has beenconfirmed that estrogen correlates with endometrial carcinoma. The biologic effectsof estrogen are effected through its binding with estrogen receptors (ER) which areligand-activated transcription factors that regulate estrogen effects in steroidhormone-targeted tissues. Estrogen receptors have two subtypes:ERαand ERβ.Matrix metalloproteinases are a proteolytic enzyme family which can degradethe extracellular matrix. Matrix metalloproteinase-26is a new member of the matrixmetalloproteinase family which was firstly cloned from the cDNA library of humanendometrial carcinoma cell lines. We studied the expression of MMP-26, ER α andER β in normal, hyperplastic and neoplastic endometriums. It was concluded that theexpression of MMP-26was closely related with estrogen and had a similar expressiontrend with ER α and ER β, which demonstrated its potential role in maintaining thenormal endometrial menstrual cycles; In endometrial cancer, MMP-26highlyexpressed in precancerous and high grade endometrial cancer, its expression wasreversely correlated with the pathological grade, the higher of the grade, the lower ofthe expression. MMP-26may play an important role in the progression of endometrialcancer, especially from precancerous to cancer, and an important indicator of goodprognosis of endometrial cancer. Our recent research has shown that there is anestrogen receptor response element (ERE) in the promoter of MMP-26. Consequently,we hypothesize that the transcription of MMP-26is affected by estrogen throughbinding with ERE.To our knowledge, there is no literature to elucidate the relationship betweenestrogen, MMP-26and endometrial cancer. In this study we used endometrialcarcinoma cell lines to explore the effect of estrogen on the transcription of MMP-26.We infected the endometrial carcinoma cell lines Ishikawa and HEC-1-B with the luciferase reporter vector containing the promoter of MMP-26and then treated thecells with estrogen over different periods of time and at different concentrationgradients. Using a dual-luciferase reporter assay system to examine the function of theMMP-26promoter. We applied Real time PCR to test the expression of ERα, ERβ,MMP-26in the endometrial carcinoma cell lines. The experimental results were asfollows:1Explore the effect of estrogen on the transcription of MMP-26by using thedual-luciferase reporter assay system.We infected the endometrial carcinoma cell lines Ishikawa and HEC-1-B withthe luciferase reporter vector containing the promoter of MMP-26and then treated thecells with estrogen over different periods of time and at different concentrationgradients. We examined the function of the MMP-26promoter using a dual-luciferasereporter assay system.The result shows the promoter of MMP-26can strive theexpression of luciferase. Estrogen can regulate the expression of MMP-26inestrogen-dependent tumor cell line Ishikawa, the expression of MMP-26isestrogen-gradient dependent. Within a range to1×10-9M, MMP-26goes up withestrogen concentration, then it gets the peak and goes down. The peak of MMP-26appeared on the time5min and24hours. But in the unestrogen-dependent tumor cellline HEC-1-B,there is no relationship between estrogen and MMP-26.2Apply Real-time PCR to test the expression of ERα, ERβ, MMP-26in thetumor cell line Ishikawa.The results show the expression of MMP-26is down regulated in Ishikawa aftertreated by estrogen at high concentration gradients from1×10-6M to1×10-9M, upregulated at low concentration gradients. The result of ERαmRNA is similar toMMP-26. There is no relationship between ERβand estrogen. The result of estrogentreatment over different periods has no statistical significance. |
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