HMGB1、PCNA在子宫肌瘤中的表达及临床意义
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摘要
目的:研究子宫肌瘤组织中高迁移率族蛋白1(high mobilitygroup box 1,HMGB1)、增殖细胞核抗原(proliferating cell nuclearantigen PCNA)表达并探讨HMGB1、PCNA在子宫肌瘤发生、发展的作用。
方法:用免疫组织化学方法,检测HMGB1在子宫肌瘤组织及子宫肌瘤旁肌层组织的表达,并同法检测研究组中的PCNA的表达作为对照。
结果:1.HMGB1蛋白在子宫肌瘤组织和子宫肌瘤旁肌层组中均有不同程度的表达,阳性颗粒主要定位于细胞核中,不同研究组胞浆中有不同程度的表达。其在子宫肌瘤组织中的阳性率83.33%,细胞核中表达以“++、+++”为主,胞浆中有轻微表达:在子宫肌瘤旁肌层组织中的阳性率43.44%,细胞核中表达以“-、+、++”为主,胞浆、胞膜周围未见明显表达。经比较子宫肌瘤组织中的阳性率高,有统计学意义(P＜0.05)。根据子宫肌瘤大小分组,HMGB1的表达无差异显著性(P＞0.05),根据子宫肌瘤单发与多发分组比较,HMGB1的表达无差异显著性(P＞0.05)。2.PCNA的阳性颗粒定位于细胞核中,胞浆、胞膜周围未见明显表达。子宫肌瘤组织、肌瘤旁肌层组织PCNA阳性表达率分别为93.33%、46.67%,二者比较有显著差异(P＜0.05)。根据子宫肌瘤大小分组比较,子宫肌瘤单发与多发分组比较,PCNA的阳性表达均无差异显著性(P＞0.05)。3.子宫肌瘤组HMGB 1的表达与PCNA的表达相关性研究rs=1,呈正相关,P＜0.05,有统计学意义。
结论:
1.子宫肌瘤与子宫肌瘤旁肌层组织均有HMGB1与PCNA的表达,提示两者在子宫肌细胞中是普遍存在的。
2.HMGB1在子宫肌瘤组织细胞核中高表达,提示细胞核中HMGB1的高表达在子宫肌瘤的发生发展中有一定作用。
3.本实验中得出子宫肌瘤中HMGB1与PCNA表达呈正相关,进一步证明细胞核内表达的HMGB1蛋白量与细胞的增生程度呈正相关。提示:核HMGB1蛋白促进细胞增殖的作用可能是子宫肌瘤的发病机制之一。
4.子宫肌瘤组织中HMGB1蛋白的高表达以细胞核内为主。这种特点将有可能指导临床肿瘤的预防、诊断、治疗:如阻断、拮抗HMGB1在核内的作用路径可能对子宫肌瘤的预防治疗有作用。
Objective: To determine the expression of high mobility group box 1(HMGB 1) and proliferating cell nuclear antigen (PCNA) in the uterine leiomyoma and the control groups ,and to investigate the role of HMGB1 in the pathogenesis of uterine leiomyoma .
Methods: Immunohistochemical method was employed to detect the expression of HMGB1 in the uterine leiomyoma and the other groups, the same methods to detect the expression of PCNA as a control. Result: 1.There were some certain extent expression of HMGB1 and PCNA in the uterine leiomyoma and the control group .Compared with the relative normal group (normal myometrium by side of leiomyoma), the positive expression of HMGB1 and PCNA in the uterine leiomyoma were significantly higher (p<0.05). 2.There was no significant difference for positive expression of HMGB1 between single leiomyoma and multiple leiomyoma,( p>0.05), the same as the expression of PCNA . There was no significant difference for positive expression of HMGB1 between the small leiomyoma and the big one, (p>0.05) .the same as the PCNA. 3.The expression of HMGB1 and PCNA was positive correlation,(rs =1 , p>0.05).
Conclusion: 1. Both HMGB1 and PCNA are expressed in every group suggests that: their existence is widespread. 2. The high expression of HMGB1 in uterine leiomyoma indicates HMGB1 is related with the development of the uterine leiomyoma. 3. The positive correlation between HMGB1 and PCNA suggest that HMGB1 is related with cell proliferation. And this relationship maybe one of the etiology of the uterine leiomyoma . 4. The positive expression of HMGB1 was mostly located and in the cell karyon in uterine leiomyoma. This character maybe direct new methods to prevent, diagnose, treat uterine leiomyoma.
方法:用免疫组织化学方法,检测HMGB1在子宫肌瘤组织及子宫肌瘤旁肌层组织的表达,并同法检测研究组中的PCNA的表达作为对照。
结果:1.HMGB1蛋白在子宫肌瘤组织和子宫肌瘤旁肌层组中均有不同程度的表达,阳性颗粒主要定位于细胞核中,不同研究组胞浆中有不同程度的表达。其在子宫肌瘤组织中的阳性率83.33%,细胞核中表达以“++、+++”为主,胞浆中有轻微表达:在子宫肌瘤旁肌层组织中的阳性率43.44%,细胞核中表达以“-、+、++”为主,胞浆、胞膜周围未见明显表达。经比较子宫肌瘤组织中的阳性率高,有统计学意义(P＜0.05)。根据子宫肌瘤大小分组,HMGB1的表达无差异显著性(P＞0.05),根据子宫肌瘤单发与多发分组比较,HMGB1的表达无差异显著性(P＞0.05)。2.PCNA的阳性颗粒定位于细胞核中,胞浆、胞膜周围未见明显表达。子宫肌瘤组织、肌瘤旁肌层组织PCNA阳性表达率分别为93.33%、46.67%,二者比较有显著差异(P＜0.05)。根据子宫肌瘤大小分组比较,子宫肌瘤单发与多发分组比较,PCNA的阳性表达均无差异显著性(P＞0.05)。3.子宫肌瘤组HMGB 1的表达与PCNA的表达相关性研究rs=1,呈正相关,P＜0.05,有统计学意义。
结论:
1.子宫肌瘤与子宫肌瘤旁肌层组织均有HMGB1与PCNA的表达,提示两者在子宫肌细胞中是普遍存在的。
2.HMGB1在子宫肌瘤组织细胞核中高表达,提示细胞核中HMGB1的高表达在子宫肌瘤的发生发展中有一定作用。
3.本实验中得出子宫肌瘤中HMGB1与PCNA表达呈正相关,进一步证明细胞核内表达的HMGB1蛋白量与细胞的增生程度呈正相关。提示:核HMGB1蛋白促进细胞增殖的作用可能是子宫肌瘤的发病机制之一。
4.子宫肌瘤组织中HMGB1蛋白的高表达以细胞核内为主。这种特点将有可能指导临床肿瘤的预防、诊断、治疗:如阻断、拮抗HMGB1在核内的作用路径可能对子宫肌瘤的预防治疗有作用。
Objective: To determine the expression of high mobility group box 1(HMGB 1) and proliferating cell nuclear antigen (PCNA) in the uterine leiomyoma and the control groups ,and to investigate the role of HMGB1 in the pathogenesis of uterine leiomyoma .
Methods: Immunohistochemical method was employed to detect the expression of HMGB1 in the uterine leiomyoma and the other groups, the same methods to detect the expression of PCNA as a control. Result: 1.There were some certain extent expression of HMGB1 and PCNA in the uterine leiomyoma and the control group .Compared with the relative normal group (normal myometrium by side of leiomyoma), the positive expression of HMGB1 and PCNA in the uterine leiomyoma were significantly higher (p<0.05). 2.There was no significant difference for positive expression of HMGB1 between single leiomyoma and multiple leiomyoma,( p>0.05), the same as the expression of PCNA . There was no significant difference for positive expression of HMGB1 between the small leiomyoma and the big one, (p>0.05) .the same as the PCNA. 3.The expression of HMGB1 and PCNA was positive correlation,(rs =1 , p>0.05).
Conclusion: 1. Both HMGB1 and PCNA are expressed in every group suggests that: their existence is widespread. 2. The high expression of HMGB1 in uterine leiomyoma indicates HMGB1 is related with the development of the uterine leiomyoma. 3. The positive correlation between HMGB1 and PCNA suggest that HMGB1 is related with cell proliferation. And this relationship maybe one of the etiology of the uterine leiomyoma . 4. The positive expression of HMGB1 was mostly located and in the cell karyon in uterine leiomyoma. This character maybe direct new methods to prevent, diagnose, treat uterine leiomyoma.
引文
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[2]Gao Z,Matsuo H,Wang Y,et al.Up-regulation by IGF-I of proliferating cell nuclear antigen and Bcl-2 protein expression in human uterine leiomyoma cells[J].J Clin Endocrinol Metab,2001,86(11):5593-5599.
[3]陈文雪,李彦群,吴小华,等.子宫肌瘤细胞凋亡及增殖状况研究Ⅱ.中国实用妇科与产科杂志,2003,19(10):603-605.
[4]Flake GP,Andersen J,Dixon D.Etiology and pathogenesis of uterine Leiomyomas:a review.Environ Health Perspect 2003;111:1037-54.
[5]Bustin,M.Regulation of DNA-dependent activities by the functional motifs of the high-mobility group chromosomal proteins.Mol.Cell.Biol.1999,19,5237-5246.
[6]Bianchi,M.E.& Beltrame,M.Upwardly mobile proteins.The role of HMG proteins in chromatin structure,gene expression and neoplasia.EMBO Rep.1,109-114(2000).
[7]Wang,H.et al.HMG-1 as a late mediator of endotoxin lethality in mice.Science 1999,285,248-251.
[8]Abraham,E.,Arcaroli,J.,Carmody,A.,Wang,H.&Tracey,K.J.HMG-1 as a mediator of acute lung inflammation.J.Immunol.2000,165,2950-2954.
[9]Andersson,U.et al.High Mobility Group 1 protein(HMG-1)stimulates pro-inflammatory cytokine synthesis in human mono-cytes.J.Exp.Med.2000,192,565-570.
[10]Seyedin SM,Pehrson JR,Cole RD.Loss of chromosomal high mobility group proteins HMG1 and HMG2 when mouse neuroblastoma and Friend erythroleukemia cells become committed to differentiation.Proc Natl Acad Sci USA 1981;78:5988-92.
[11]Muller S,Ronfani L,Bianchi ME(SanRaffaele Scientific Institute;and San Raffaele University,Milan,Italy).Regulated expression and sub cellular localization of HMGB1,a chromatin protein with a cytokine function(Mini symposium).J Intern Med 2004;255:332-343.
[12]Goodwin GH,Sanders C,Johns EW.A new group of chromatin-Associated proteins with a high content of acidic and basic amino acids.Eur J Biochem 1973;38:14-19.
[13]Xiang YY,Wang DY,Tanaka Met al.Expression of high mobility group-1 mRNA in human gastrointestinal adenocarcinoma and corresponding non- cancerous mucosa.Int J Cancer 1997;74:1-6.
[14]Kuniyasu H,Chihara Y,Takahashi T.Co-expression of receptor for advanced glycation end products and the ligand amphoterin associates closely with metastasis of colorectal cancer[J].Oncol Rep,2003,10(2):445-448.
[15]Ranganna K,Yousefipour Z,Yatsu FM,et al.Gene expression profile of butyrate-inhibited vascular smooth muscle cell proliferation[J].Mol Cell Biochem,2003,254(1-2):21-36.
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