The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of...The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.展开更多
Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Met...Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Methods:The effect of genistein on MMP-26 and ERa expression was examined by western blot in cultured Ishikawa and HEC-1B cells.Additionally,the effects of genistein on ERa-ERE-luc and ERb-ERE-luc reporter gene expression in HEC-1B cells were analyzed by luciferase activity assays.Results:MMP-26 and ERa protein expression was down-regulated by genistein treatment in Ishikawa cell induced by high concentration E2,whereas MMP-26 and ERa protein expression was up-regulated by genistein treatment in Ishikawa cells induced by low concentration E2.Expression of the ERa-ERE-luc and ERb-ERE-luc reporter genes was significantly increased after E2 induction and was further up-regulated by genistein.Expression of ERa-ERE-luc and ERb-ERE-luc reporter genes decreased significantly following genistein treatment in high E2 concentrations,and increased significantly following genistein treatment in low E2 concentrations.Conclusions:Genistein showed estrogen-like effects in endometrial cancer cells and influenced estrogen receptor signaling by modulating ERa and ERb expression.展开更多
Matrix metalloproteinase-26 (MMP-26, endo-metase and matrilysin-2), a novel member of the MMPs family, is detected not only in the placenta and uterus, but is widely expressed in malignant tumors from different source...Matrix metalloproteinase-26 (MMP-26, endo-metase and matrilysin-2), a novel member of the MMPs family, is detected not only in the placenta and uterus, but is widely expressed in malignant tumors from different sources as well as in diverse tumor cell lines. However, the function of MMP-26 in the reproductive system has never been reported. Expression of MMP-26 in mouse embryos and the function of the MMP-26 antibody during mouse embryo implantation was examined for the first time by injecting the uterine horn, immunohistochemistry, in situ hybridization, co-culture of mouse blastocysts and uterine monolayer epithelial cells, Western blot, RT-PCR, Northern blot and zymography. Our results show that there is strong expression of MMP-26 niRNA and protein in the mouse embryo. Furthermore, the MMP-26 antibody dramatically inhibited mouse embryo implantation and significantly inhibited adhesion and outgrowth of mouse blastocysts on in vitro uterine monolayer epithelial cells. At the same time, the MMP-26展开更多
文摘The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.
基金by National Nature Funds(No.30510403202)National Ministry of Education(No.IRT0413)Doctor Funds supported by National Ministry of Education(No.20050026012 and 20060026019).
文摘Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Methods:The effect of genistein on MMP-26 and ERa expression was examined by western blot in cultured Ishikawa and HEC-1B cells.Additionally,the effects of genistein on ERa-ERE-luc and ERb-ERE-luc reporter gene expression in HEC-1B cells were analyzed by luciferase activity assays.Results:MMP-26 and ERa protein expression was down-regulated by genistein treatment in Ishikawa cell induced by high concentration E2,whereas MMP-26 and ERa protein expression was up-regulated by genistein treatment in Ishikawa cells induced by low concentration E2.Expression of the ERa-ERE-luc and ERb-ERE-luc reporter genes was significantly increased after E2 induction and was further up-regulated by genistein.Expression of ERa-ERE-luc and ERb-ERE-luc reporter genes decreased significantly following genistein treatment in high E2 concentrations,and increased significantly following genistein treatment in low E2 concentrations.Conclusions:Genistein showed estrogen-like effects in endometrial cancer cells and influenced estrogen receptor signaling by modulating ERa and ERb expression.
基金This work was supported in part by the Special Fund for the State Key Basic Research Projects (Grant No. G1999055903)the National Natural Science Foundation of China (Grant No. 30170357)the 100-Scientist-Program of the Chinese Academy of Sciences
文摘Matrix metalloproteinase-26 (MMP-26, endo-metase and matrilysin-2), a novel member of the MMPs family, is detected not only in the placenta and uterus, but is widely expressed in malignant tumors from different sources as well as in diverse tumor cell lines. However, the function of MMP-26 in the reproductive system has never been reported. Expression of MMP-26 in mouse embryos and the function of the MMP-26 antibody during mouse embryo implantation was examined for the first time by injecting the uterine horn, immunohistochemistry, in situ hybridization, co-culture of mouse blastocysts and uterine monolayer epithelial cells, Western blot, RT-PCR, Northern blot and zymography. Our results show that there is strong expression of MMP-26 niRNA and protein in the mouse embryo. Furthermore, the MMP-26 antibody dramatically inhibited mouse embryo implantation and significantly inhibited adhesion and outgrowth of mouse blastocysts on in vitro uterine monolayer epithelial cells. At the same time, the MMP-26
