【摘要】：目的：①系統(tǒng)性研究PIM家族激酶(PIM-1/-2/-3)在前列腺癌與良性前列腺增生組織及前列腺細胞系中的表達情況。②明確PIM激酶在前列腺癌中的表達水平與其臨床相關(guān)性。③探討PIM激酶是否通過其激酶結(jié)構(gòu)域在前列腺癌的發(fā)生發(fā)展中發(fā)揮作用。 方法：收集2000年1月到2012年6月在天津醫(yī)科大學(xué)第二醫(yī)院經(jīng)病理診斷確診為前列腺癌的160例患者的術(shù)中癌組織和100例良性前列腺增生組織標本,所有前列腺癌患者術(shù)前均未接受內(nèi)分泌治療以及放化療。培養(yǎng)前列腺癌細胞系LNCaP及PC3,正常前列腺上皮細胞系RWPE-1.采用組織總RNA提取、cDNA合成、RT-qPCR以及Western Blot等技術(shù),分析PIM激酶在前列腺癌與良性前列腺增生組織及前列腺細胞系中的表達水平,并研究其表達水平與前列腺癌臨床病理特征以及前列腺癌患者PSA生化復(fù)發(fā)的相關(guān)性。 結(jié)果：①PIM-1/-2/-3在前列腺癌組織中的mRNA表達水平均顯著高于良性前列腺增生組織(P0.05)；②PIM-1/-2/-3在前列腺癌細胞系中蛋白表達水平均顯著高于正常前列腺上皮細胞(P0.05)；③PIM-1/-2/-3的高表達與血清前列腺特異性抗原(PSA),較高的Gleason評分,高級別腫瘤病理分期(T3),淋巴結(jié)浸潤及神經(jīng)周圍浸潤有關(guān)(P0.05)；④PIM-1/-2/-3的高表達與患者的年齡,手術(shù)切緣陽性以及精囊侵犯沒有必然的聯(lián)系(P0.05)；⑤PIM-1/-2/-3的高表達與前列腺癌患者PSA生化復(fù)發(fā)有關(guān),具有統(tǒng)計學(xué)意義(P0.05)。 結(jié)論：①PIM家族激酶所有三個成員在前列腺癌中的表達均顯著高于良性前列腺增生組織以及正常前列腺上皮細胞,表明其共同的組織分布特性；②PIM家族激酶的高表達均與前列腺癌的發(fā)生和進展具有相關(guān)性,表明其存在相近的生理特性；③PIM激酶在前列腺癌中可能通過其激酶結(jié)構(gòu)域發(fā)揮作用,PIM蛋白激酶結(jié)構(gòu)域可能成為研究前列腺癌發(fā)病機制的一個重要突破點,并成為治療前列腺癌的一個潛在靶點,但還有待于進一步研究。
[Abstract]:Objective: 1 to systematically study the expression of PIM family kinase (PIM-1/-2/-3) in prostate cancer and benign prostatic hyperplasia (BPH) tissues and prostatic cell lines. To investigate whether PIM kinase plays a role in the development of prostate cancer through its kinase domain. Methods: from January 2000 to June 2012, 160 cases of prostate cancer and 100 cases of benign prostatic hyperplasia were collected from the second Hospital of Tianjin Medical University. All patients with prostate cancer were not treated with endocrine therapy or radiotherapy and chemotherapy before operation. Culture of Prostate Cancer Cell Line LNCaP and PC3, normal Prostate epithelial Cell Line RWPE-1. Total RNA extraction, cDNA synthesis, RT-qPCR and Western Blot were used to analyze the expression of PIM kinase in prostate cancer and benign prostatic hyperplasia (BPH) and prostatic cell line. To study the correlation between the expression level and clinicopathological features of prostate cancer and the biochemical recurrence of PSA in patients with prostate cancer. Results: the mRNA expression of 1PIM-1/-2/-3 in prostate cancer was significantly higher than that in benign prostatic hyperplasia (P0.05), and the expression of 2PIM-1/-2/-3 in prostate cancer cell line was significantly higher than that in normal prostatic epithelial cell (P0.05). The high expression of 3PIM-1/-2/-3 was related to the higher Gleason score of serum prostate specific antigen (PSA), the pathological stage of high grade tumor (T3), lymph node invasion and peripheral nerve infiltration (P0.05), the high expression of 4PIM-1/-2/-3 was associated with the age of the patients. The positive margin of surgical incision and seminal vesicle invasion were not associated (P0.05); the high expression of 5PIM-1/-2/-3 was related to the recurrence of PSA in prostate cancer patients with statistical significance (P0.05). Conclusion: the expression of all three members of 1PIM family kinase in prostate cancer is significantly higher than that in benign prostatic hyperplasia and normal prostatic epithelial cells, indicating their common tissue distribution characteristics. The high expression of 2PIM family kinases was associated with the occurrence and progression of prostate cancer, indicating that there were similar physiological characteristics. 3PIM kinase may play a role in prostate cancer through its kinase domain. PIM protein kinase domain may become an important breakthrough point in studying the pathogenesis of prostate cancer and a potential target for the treatment of prostate cancer. But it still needs further study.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.25

【參考文獻】

相關(guān)期刊論文 前1條

1 韓蘇軍;張思維;陳萬青;李長嶺;;中國前列腺癌發(fā)病現(xiàn)狀和流行趨勢分析[J];臨床腫瘤學(xué)雜志;2013年04期

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本文編號：2270329