【摘要】：目的了解p-Stat3、p-Akt及其下游靶基因cyclinD1蛋白在Paget病中的表達(dá),進(jìn)一步探討Stat3信號轉(zhuǎn)導(dǎo)通路和Akt信號轉(zhuǎn)導(dǎo)通路在Paget病發(fā)生、發(fā)展中的作用。 方法應(yīng)用免疫組化技術(shù)檢測21例Paget病(其中乳房Paget病12例,乳房外Paget病9例)、15例汗管瘤及10例正常皮膚標(biāo)本中的p-Stat3、p-Akt和cyclinD1蛋白的表達(dá),采用圖像分析系統(tǒng)測定標(biāo)本中p-Stat3、p-Akt和cyclinD1陽性表達(dá)的平均光密度值,并對這三種蛋白的表達(dá)進(jìn)行相關(guān)性分析。 結(jié)果(1)在Paget病、汗管瘤和正常皮膚組織標(biāo)本中,p-Stat3蛋白表達(dá)的平均光密度值分別為：0.354±0.039、0.172±0.034、0.174±0.025,Paget病中p-Stat3蛋白的表達(dá)水平顯著升高,與汗管瘤和正常皮膚組織中的表達(dá)比較差異有統(tǒng)計學(xué)意義(P0.001),汗管瘤和正常皮膚組織中的表達(dá)比較差異無統(tǒng)計學(xué)意義(P0.05);p-Akt蛋白表達(dá)的平均光密度值分別為0.299±0.042、0.167±0.028、0.174±0.029,Paget病中p-Akt蛋白的表達(dá)水平顯著升高,與汗管瘤和正常皮膚組織中的表達(dá)比較差異有統(tǒng)計學(xué)意義(P0.001),汗管瘤和正常皮膚組織中的表達(dá)比較差異無統(tǒng)計學(xué)意義(P0.05);cyclinD1蛋白表達(dá)的的平均光密度值分別為0.406±0.046、0.172±0.035、0.171±0.016,Paget病中cyclinD1蛋白的表達(dá)水平顯著升高,與汗管瘤和正常皮膚組織中的表達(dá)比較差異有統(tǒng)計學(xué)意義(P0.001),汗管瘤和正常皮膚組織中的表達(dá)比較差異無統(tǒng)計學(xué)意義(P0.05)。(2)乳房與乳房外Paget病比較,p-Stat3、p-Akt和cyclinD1蛋白的表達(dá)差異無統(tǒng)計學(xué)意義(P均0.05)。(3)在paget病中,p-Stat3與cyclinD1的表達(dá)呈正相關(guān)(r=0.809,P0.05),p-Akt與cyclinD1的表達(dá)呈正相關(guān)(Υ=0.776, P＜0.05);p-Stat3與p-Akt的表達(dá)呈正相關(guān)(r=0.516,P0.05)。 結(jié)論(1)Paget病皮損中存在p-Stat3、p-Akt和cyclinD1的過度表達(dá),提示JAK/Stat3信號轉(zhuǎn)導(dǎo)通路和PI3K/Akt信號轉(zhuǎn)導(dǎo)通路在Paget病中被激活,可能在Paget病的發(fā)生、發(fā)展過程中起重要作用；(2)p-Stat3、p-Akt可能通過JAK/Stat3信號轉(zhuǎn)道通路及PI3K/Akt信號轉(zhuǎn)道通路誘導(dǎo)cyclinD1的過度表達(dá),促使腫瘤細(xì)胞的生長及增殖。
[Abstract]:Objective to investigate the expression of p-Stat3pAkt and its downstream target gene cyclinD1 protein in Paget disease and to explore the role of Stat3 signal transduction pathway and Akt signal transduction pathway in the pathogenesis and development of Paget disease. Methods Immunohistochemical technique was used to detect the expression of p-Stat3pAkt and cyclinD1 protein in 21 cases of Paget's disease (including 12 cases of Paget's disease of breast and 9 cases of extramammary Paget disease), 15 cases of hyperhidroma and 10 cases of normal skin. The average optical density of p-Stat3pAkt and cyclinD1 positive expression was measured by image analysis system, and the correlation of the expression of these three proteins was analyzed. Results (1) the average optical density of the expression of p-Stat3 protein in Paget's disease, histopathoma and normal skin tissues was 0.354 鹵0.039 鹵0.172 鹵0.034 鹵0.174 鹵0.025 respectively. There was a significant difference between the expression of histopathoma and normal skin tissue (P0.001), but there was no significant difference in the expression of hyperhidroma and normal skin tissue (P0.05). The average optical density of expression of p-Akt protein was 0.299 鹵0.042, 0.167 鹵0.028, 0.174 鹵0.029, respectively. The expression of p-Akt protein was significantly increased in Paget's disease. There was a significant difference between the expression of histopathoma and normal skin tissue (P0.001), but there was no significant difference in the expression of hyperhidroma and normal skin tissue (P0.05). The average optical density of expression of cyclinD1 protein was 0.406 鹵0.046 鹵0.172 鹵0.035 鹵0.171 鹵0.016 in paget's disease, and the expression of cyclinD1 protein was significantly higher than that in hyperhidroma and normal skin tissues (P0.001). There was no significant difference in the expression of p-Stat3 between Paget's disease of breast and that of extramammary Paget disease (P0.05). (2), and there was no significant difference in the expression of p-Stat3 between hyperhidroma and normal skin tissue (P0.05). There was no significant difference between the expression of p-Akt and cyclinD1 protein in paget disease (P < 0. 05). In paget disease, the expression of p-Stat3 and cyclinD1 was positively correlated (r = 0. 809 P 0.05), and the expression of p-Akt and cyclinD1 was positively correlated (r = 0. 776, P < 0. 05). P < 0.05); There was a positive correlation between the expression of p-Stat3 and p-Akt (P 0.05). Conclusion (1) the overexpression of p-Stat3pAkt and cyclinD1 in the lesions of Paget disease suggests that JAK/Stat3 signal transduction pathway and PI3K/Akt signal transduction pathway are activated in Paget disease, which may play an important role in the occurrence and development of Paget disease. (2) p-Stat3or p-Akt may induce the overexpression of cyclinD1 through JAK/Stat3 signaling pathway and PI3K/Akt signaling pathway, and promote the growth and proliferation of tumor cells.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R739.5

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