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Effect Of Down-regulation Of SOX2 Expression On ER? In Prostate Cancer DU-145 Cells

Posted on:2020-03-01Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y SongFull Text:PDF
GTID:2404330575457740Subject:Pathology and pathophysiology
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BackgroundProstate cancer is one of the most common malignant tumors in men with morbidity and mortality,and is the sixth most common cancer in the world.In recent years,the incidence and mortality of prostate cancer in China has increased year by year.During treatment,some patients who are sensitive to hormone therapy eventually evolve into hormone-independent prostate cancer,which may be related to the amplification and mutation of androgen receptor genes and cancer stem cells.SOX2 is a member of the SOX family and is essential for maintaining the self-renewal and pluripotency of embryonic stem cells.SOX2 is located on chromosome 3,and SOX2 functions as a regulatory gene,which is related to its HMG-box domain,and has a transcriptional activation function at its C-terminus.Overexpression of SOX2 is associated with breast cancer,small cell lung cancer,and papillary thyroid carcinoma.SOX2 expression is also significantly elevated in prostate cancer with high malignancy.ER? is the second subtype of the estrogen receptor and belongs to the nuclear hormone receptor(NHR)family of proteins that play an important role in cell growth.The study found that ER? is down-regulated and absent in breast cancer,lung cancer,ovarian cancer,and colorectal cancer.ER? is expressed in normal prostate epithelium,and ER? expression is also down-regulated in prostate cancer,especially in prostate cancer with bone metastasis and lymph node metastasis,ER? expression is absent.In this study,we observed the expression of SOX2 and ER? in prostate cancer and benign prostatic hyperplasia by immunohistochemistry,and analyzed the relationship between SOX2 and ER? expression and clinicopathological parameters in prostate cancer tissues and the relationship between them;SOX2-shRNA Transfected prostate cancer DU-145 cells,observed the expression of ER? and the effect on cell invasion and migration after down-regulation of SOX2 expression.Methods1.Screening 60 cases of prostate cancer diagnosed between 2011 and 2013 and 20 cases of benign prostatic hyperplasia2.Immunohistochemical technique was used to detect the expression of SOX2 and ER? in prostate cancer and benign prostatic hyperplasia.3.Western Blot and qRT-PCR were used to detect the expression of SOX2 and ER? in SOX2-shRNA transfected prostate cancer cells.4.The effect of down-regulation of SOX2 expression on the migration ability of prostate cancer cells was detected by Transwell assay.5.Cell scratch test to detect the effect of down-regulation of sox2 on the invasion ability of prostate cancer cells.Results1.The expression of SOX2 is mainly localized in cytoplasm,and the nucleus of prostate cancer with high degree of malignancy is also expressed?the expression rate of prostate cancer tissue was 75%(45/60)was significantly higher than that of benign prostatic hyperplasia(20%)(4/20),And the expression of SOX2 in Gleason=3+4 and Gleason+4+3 is also different,the expression of SOX2 increased with the increase of Gleason score,The expression of SOX2 was correlated with TNM stage and survival time of patients with prostate cancer,and was not related to age and serum PSA.With the increase of TNM stage,the expression of SOX2 was significantly increased,and the survival time of patients was shortened.2.The expression of ER? was localized in the nucleus.The expression rate of prostate cancer was 36%(22/60),which was significantly lower than that of benign prostatic hyperplasia(75%)(15/20).The expression of ER? decreased with the increase of Gleason score.The expression of ER? was correlated with TNM stage and survival time of patients with prostate cancer,and was not related to the age of patients and serum PSA.With the increase of TNM stage,the expression of ER? was down-regulated,and the survival time of patients was shortened.3.After down-regulation of SOX2 expression,it can inhibit cell proliferation and invasion;up-regulate the expression of ER?.4.SOX2 was negatively correlated with the expression of ER? Conclusions1.SOX2 is up-regulated in prostate cancer tissues,and ER? is down-regulated in prostate cancer tissues;the two are negatively correlated.2.Down-regulation of SOX2 expression can inhibit the proliferation and invasion of tumor cells;its mechanism may be related to the activation of ER? expression,but the specific mechanism needs further study.
Keywords/Search Tags:prostate cancer, SOX2, ER?, invasion
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