LRP16在子宫内膜癌中的表达及临床意义
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摘要
目的：探讨LRP16在子宫内膜癌中的表达与临床病理间的关系,及LRP16与E-cadherin在子宫内膜癌中的关联。方法：随机采集临床26例子宫内膜癌组织及10例正常子宫内膜组织。(1)采用逆转录聚合链式反应方法(RT-PCR)测量LRP16mRNA在子宫内膜癌组织和正常内膜组织中的表达；(2)采用免疫组织化学SP法检测LRP16蛋白和E-cadherin在子宫内膜癌组织中的表达。结果：(1)在26例子宫内膜癌组织中LRP16mRNA呈阳性表达者21例,其阳性表达率为83.33%,表达水平0.82±0.21；10例正常组织中LRP16mRNA呈阳性表达者3例,阳性表达率为30%,表达水平0.47±0.18,两者差异有统计学意义(P=0.012,P<0.05) (2) LRP16核阳性表达率为61.54%(16／26),浆阳性表达率96.15%(25／26)。ERa阴性患者中LRP16核阳性率为85.56%,ERa阳性患者中核阳性率为52.65%。两者差异具有显著性(P<0.05)LRP16核表达与组织学分级呈正相关(P<0.05),而与手术病理分期无相关性(P>0.05), LRP16浆表达与手术病理分期呈负相关(P<0.05),而与组织学分级无相关性(P>0.05) (3) LRP16蛋白的表达水平与上皮细胞钙粘蛋白的表达差异无相关性(P>0.05)结论：子宫内膜癌中LRP16mRNA表达明显高于正常内膜组织(P<0.05),LRP16核表达提示预后不良,LRP16浆表达提示预后良好,LRP16蛋白的表达水平与上皮细胞钙粘蛋白的表达无相关性(P>0.05)
Objective:To explore the relationship of expression of LRP16 and clinicopathologic features and investgate the correlation between expression of LRP16 and E-cadherin in endometria cancer. Methods:26 endometrial cancer tissues and 10 normal endometria tissues were collected randomly. The expressions of LRP16mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR)in 26 26 endometrial cancer and 10 normal endometrium, The expression of LRP16 and E-cadherin were examined by immunohistochemistry in the 26 endometrial cancer tissues Results:(1) the positive rates of LRP16mRNA were 83.33% in endometrial cancer and 30% in normal endometrium respectively,the level of LRP16mRNA were 0.82±0.21 in endometrial cancer and 0.47±0.18 in normal endometrium respectively, the difference was significant(p<0.05) (2) the positive rates of LRP16 were 61.54% in the nucleus and the positive rates of LRP16 were 96.15% in the cytoplasm. In ERa negative endometrial cancer,LRP16 expression rates in the nucleus was 85.56%, In ERa positive endometrial cancer, LRP16 expression rates in the nucleus was 52.65%. there were no ralationship between LRP16 expression in the nucleue and staging,but it was related with grade.LRP16 expression in the cytoplasm was related with staging,but it was no related with grade (3)there was no significantly correlation between LRP16 expression and E-cadherin expression endometrial cancer (P>0.05).Conclusions:Positive rate of LRP16 in endometrial cancer was higher than in normal endometrium,LRP16 expression in the cytoplasm may be correlated with good prognosis, LRP16 expression in the nucleus may be correlated with bad prognosis there was no significantly diference betweenLRP16 expression and E-cadherin expression in endometrial cancer
Objective:To explore the relationship of expression of LRP16 and clinicopathologic features and investgate the correlation between expression of LRP16 and E-cadherin in endometria cancer. Methods:26 endometrial cancer tissues and 10 normal endometria tissues were collected randomly. The expressions of LRP16mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR)in 26 26 endometrial cancer and 10 normal endometrium, The expression of LRP16 and E-cadherin were examined by immunohistochemistry in the 26 endometrial cancer tissues Results:(1) the positive rates of LRP16mRNA were 83.33% in endometrial cancer and 30% in normal endometrium respectively,the level of LRP16mRNA were 0.82±0.21 in endometrial cancer and 0.47±0.18 in normal endometrium respectively, the difference was significant(p<0.05) (2) the positive rates of LRP16 were 61.54% in the nucleus and the positive rates of LRP16 were 96.15% in the cytoplasm. In ERa negative endometrial cancer,LRP16 expression rates in the nucleus was 85.56%, In ERa positive endometrial cancer, LRP16 expression rates in the nucleus was 52.65%. there were no ralationship between LRP16 expression in the nucleue and staging,but it was related with grade.LRP16 expression in the cytoplasm was related with staging,but it was no related with grade (3)there was no significantly correlation between LRP16 expression and E-cadherin expression endometrial cancer (P>0.05).Conclusions:Positive rate of LRP16 in endometrial cancer was higher than in normal endometrium,LRP16 expression in the cytoplasm may be correlated with good prognosis, LRP16 expression in the nucleus may be correlated with bad prognosis there was no significantly diference betweenLRP16 expression and E-cadherin expression in endometrial cancer
引文
1. Ries LAG, Melbert D, Krapcho M, eds, et al. SEER Cancer Statistics Review,1975-2005. National Cancer Institute; Bethesda, MD. http://seer. cancer.gov/csr/1975-2005/, based on November 2007 SEER data submission, posted to the SEER web site,2008.
2.韩为东,于力,楼方定,等.一个新的白血病相关基因LRP16—全长cDNA的克隆、序列分析及表达特征[J].中国生物化学与分子生物学报,2001,17(2)：58-63.
3. Han W D,Mu Y M, Lu X C, Li X J, Yu L, Song H J, U M, LuJ M, Zhan Y L, Pan C Y. Up-regulation of LRP16 mRNA by 17 B-estradiol through activation of estrogen receptor (ERa), but not ERB, and promotion human breast cancer MCF-7 cell proliferation: a preliminary report E[J]. Endocr Relat Cancer,2003,10(2):217-224.
4. U. S. Cancer Statistics Working Group,et al.United States cancer statistics:1999 incidence. Atlanta, GA:Department of HeMth and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute,2002.
5.韩为东,楼方定,于力.LRP16基因的SAGE谱及其在正常血细胞白血病细胞中的表达状况[J].军医进修学院学报,2002,23(3)：161-163.
6.于力,韩为东,楼方定,等.新的白血病基因LRP16的克隆[J].军医进修学院学报,2000,21(2)：81-84.
7. Piur B, Rabinovich A, Aizenberq N, et al.Cadherins in malignancies of the female genital tract[J].Harefuah,2005 Apr;144(4):261-5,303, 302.
8. A Jeanes, CJ Gottardi, and AS Yap, et al. Cadherins and cancer:how does cadherin dysfunction promote tumor progression? [J].Oncogene. 2008,27(55):6920-6929.
9.韩为东,孟元光, 廖代祥,等.LRP16通过调控E-钙黏着蛋白的表达促进MCF-7细胞的侵袭生长[J].中国生物化学与分子生物学报2006,22(9)：724-732.
10.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980-983.
11.卢学春,楼方定,韩卫东,等,LRP16基因启动子顺式调控元件分析[J].生物信息学,2009,7(1)：5-8.
12.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980-983.
13. Mell LK, Meyer JJ, Tretiakova M, et al. Function of estrogen-related receptor alpha in human endometrial cancer[J]. Clin Cancer Res, 2004,10(16):5546-5553.
14. Talvensaari-Mattila A, Santala M, Soini Y, et al. Prognostic value of matrix metalloproteinase-2(MMP-2) expression in endometrial endometrioidadenocarcinoma[J].AnticancerRes,2005,25(6B):4101-41 05.
15.Aglund K, Rauvala M, Puistola U, et al. Gelatinases A and B (MMP-2 and MMP-9)in endometrial cancer-MMP-9 correlates to the grade and the stage[J].Gynecol Oncol,2004,94(3):699-704.
16.孟元光,韩为东,赵亚力,等.LRP16基因通过雌激素受体介导抑制Ishikawa细胞中E—钙黏着素的转录激活[J].生物技术通讯,2007,18(3)：368-370.
17.Meng Y G, Han W D, Zhao YL, et al. Induction of LRP 16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the down regulation of E-cadherin [J].Cell Res,2007,17(10):869-880.
18.尹肖云,孟元光,赵亚力,等.人类白血病相关性基因LRP16及与肿瘤关系的研究进展[J].现代肿瘤医学,2008,10(10)：1840-1843.
19.赵亚力,韩为东,母义明,等.雌激素通过ERa与Spl的相互作用上调LRP16基因的转录[J].中国生物化学与分子生物学,2004,20： 99-105.
20. Liao DX, Han WD, Zhao YL, et al. The expression and dinical significance of the LRP 16 gene in human breast cancer[J]. Chin J Cancer,2006,25:44-49.
21.Maddugoda MP, Crampton MS, Shewan AM, Yap AS. Myosin VI and vinculin cooperate during themorphogenesis of cadherin cell-cell contacts in mammalian epithelial cells. [J].Cell Bio 2007; 178: 529-540.
22. Nejsum LN, Nelson WJ. A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity [J]. Cell Biol 2007; 178:323-335.
23. Lee M, Vasioukhin V. Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. [J].Cell Sci 2008;121:1141-1150.
24.田丽媛,赵亚力,韩为东,孟元光,等.卵巢上皮肿瘤中LRP16蛋白表达的意义及其与ER、PR、E—cadherin的关系[J].现代肿瘤医学,2008,16(4)：629-632.
1.于力,韩为东,楼方定,等.新的白血病基因LRP16的克隆[J].军医进修学院学报,2000,21(2)：81-84.
2.韩为东,于力,楼方定,等.一个新的白血病相关基因LRP16—全长cDNA的克隆、序列分析及表达特征[J].中国生物化学与分子生物学报,2001,17(2)：58-63.
3.韩为东,楼方定,于力.LRP16基因的SAGE谱及其在正常血细胞白血病细胞中的表达状况[J].军医进修学院学报,2002,23(3)：161-163.
4.卢学春,楼方定,韩卫东,等,LRP16基因启动子顺式调控元件分析[J].生物信息学,2009,7(1)：5—8.
5.韩为东,母义明,宋海静,等.雌激素上调LRP16基因表达的研究[J].军医进修学院学报,2003,24(3)：196-198.
6. Zhao YL, Han WD, Li Q, et al. Mechanism of transcriptional regulation of LRPI6 gene expression by 17-beta estradiol in MCF-7 human breast cells[J].J Mol Endocrinol,2005,34(1):77-89.
7. U. S. Cancer Statistics Working Group. United States cancer statistics:1999 incidence. Atlanta, GA:Department of HeMth and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute,2002
8.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980—983.
9. Mell LK, Meyer JJ, Tretiakova M, et al. Function of estrogen-related receptor alpha in human endometrial cancer[J]. Clin Cancer Res,2004,10(16):5546-5553.
10. Talvensaari-Mattila A, Santala M, Soini Y, et al. Prognostic value of matrix metalloproteinase-2 (MMP-2)expression in endometrial endometrioid adenocarcinoma [J].Anticancer Res,花2005,25(6B): 4101-4105.
11.Aglund K, Rauvala M, Puistola U, et al. Gelatinases A and B (MMP-2 and MMP-9)in endometrial cancer- MMP-9 correlates to the grade and the stage[J].Gynecol Oncol,2004,94(3):699-704.
12.尹肖云,孟元光,赵亚力,等.人类白血病相关性基因LRP16及与肿瘤关系的研究进展[J].现代肿瘤医学,2008,10(10)：1840—1843.
13.孟元光,韩为东,赵亚力,等.LRP16基因通过雌激素受体介导抑制Ishikawa细胞中E—钙黏着素的转录激活[J].生物技术通讯,2007,18(3)：368—370.
14. Meng YG, Han W D, Zhao YL, et al. Induction of LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the down regulation of E-cadherin[J]. Cell Res,2007,17(10):869-880.
15.陈美霞,孟元光,韩为东,等.LRPI6基因在子宫内膜样腺癌中的表达及意义[J].现代妇产科进展,2007,16(5)：374—377.
2.韩为东,于力,楼方定,等.一个新的白血病相关基因LRP16—全长cDNA的克隆、序列分析及表达特征[J].中国生物化学与分子生物学报,2001,17(2)：58-63.
3. Han W D,Mu Y M, Lu X C, Li X J, Yu L, Song H J, U M, LuJ M, Zhan Y L, Pan C Y. Up-regulation of LRP16 mRNA by 17 B-estradiol through activation of estrogen receptor (ERa), but not ERB, and promotion human breast cancer MCF-7 cell proliferation: a preliminary report E[J]. Endocr Relat Cancer,2003,10(2):217-224.
4. U. S. Cancer Statistics Working Group,et al.United States cancer statistics:1999 incidence. Atlanta, GA:Department of HeMth and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute,2002.
5.韩为东,楼方定,于力.LRP16基因的SAGE谱及其在正常血细胞白血病细胞中的表达状况[J].军医进修学院学报,2002,23(3)：161-163.
6.于力,韩为东,楼方定,等.新的白血病基因LRP16的克隆[J].军医进修学院学报,2000,21(2)：81-84.
7. Piur B, Rabinovich A, Aizenberq N, et al.Cadherins in malignancies of the female genital tract[J].Harefuah,2005 Apr;144(4):261-5,303, 302.
8. A Jeanes, CJ Gottardi, and AS Yap, et al. Cadherins and cancer:how does cadherin dysfunction promote tumor progression? [J].Oncogene. 2008,27(55):6920-6929.
9.韩为东,孟元光, 廖代祥,等.LRP16通过调控E-钙黏着蛋白的表达促进MCF-7细胞的侵袭生长[J].中国生物化学与分子生物学报2006,22(9)：724-732.
10.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980-983.
11.卢学春,楼方定,韩卫东,等,LRP16基因启动子顺式调控元件分析[J].生物信息学,2009,7(1)：5-8.
12.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980-983.
13. Mell LK, Meyer JJ, Tretiakova M, et al. Function of estrogen-related receptor alpha in human endometrial cancer[J]. Clin Cancer Res, 2004,10(16):5546-5553.
14. Talvensaari-Mattila A, Santala M, Soini Y, et al. Prognostic value of matrix metalloproteinase-2(MMP-2) expression in endometrial endometrioidadenocarcinoma[J].AnticancerRes,2005,25(6B):4101-41 05.
15.Aglund K, Rauvala M, Puistola U, et al. Gelatinases A and B (MMP-2 and MMP-9)in endometrial cancer-MMP-9 correlates to the grade and the stage[J].Gynecol Oncol,2004,94(3):699-704.
16.孟元光,韩为东,赵亚力,等.LRP16基因通过雌激素受体介导抑制Ishikawa细胞中E—钙黏着素的转录激活[J].生物技术通讯,2007,18(3)：368-370.
17.Meng Y G, Han W D, Zhao YL, et al. Induction of LRP 16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the down regulation of E-cadherin [J].Cell Res,2007,17(10):869-880.
18.尹肖云,孟元光,赵亚力,等.人类白血病相关性基因LRP16及与肿瘤关系的研究进展[J].现代肿瘤医学,2008,10(10)：1840-1843.
19.赵亚力,韩为东,母义明,等.雌激素通过ERa与Spl的相互作用上调LRP16基因的转录[J].中国生物化学与分子生物学,2004,20： 99-105.
20. Liao DX, Han WD, Zhao YL, et al. The expression and dinical significance of the LRP 16 gene in human breast cancer[J]. Chin J Cancer,2006,25:44-49.
21.Maddugoda MP, Crampton MS, Shewan AM, Yap AS. Myosin VI and vinculin cooperate during themorphogenesis of cadherin cell-cell contacts in mammalian epithelial cells. [J].Cell Bio 2007; 178: 529-540.
22. Nejsum LN, Nelson WJ. A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity [J]. Cell Biol 2007; 178:323-335.
23. Lee M, Vasioukhin V. Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. [J].Cell Sci 2008;121:1141-1150.
24.田丽媛,赵亚力,韩为东,孟元光,等.卵巢上皮肿瘤中LRP16蛋白表达的意义及其与ER、PR、E—cadherin的关系[J].现代肿瘤医学,2008,16(4)：629-632.
1.于力,韩为东,楼方定,等.新的白血病基因LRP16的克隆[J].军医进修学院学报,2000,21(2)：81-84.
2.韩为东,于力,楼方定,等.一个新的白血病相关基因LRP16—全长cDNA的克隆、序列分析及表达特征[J].中国生物化学与分子生物学报,2001,17(2)：58-63.
3.韩为东,楼方定,于力.LRP16基因的SAGE谱及其在正常血细胞白血病细胞中的表达状况[J].军医进修学院学报,2002,23(3)：161-163.
4.卢学春,楼方定,韩卫东,等,LRP16基因启动子顺式调控元件分析[J].生物信息学,2009,7(1)：5—8.
5.韩为东,母义明,宋海静,等.雌激素上调LRP16基因表达的研究[J].军医进修学院学报,2003,24(3)：196-198.
6. Zhao YL, Han WD, Li Q, et al. Mechanism of transcriptional regulation of LRPI6 gene expression by 17-beta estradiol in MCF-7 human breast cells[J].J Mol Endocrinol,2005,34(1):77-89.
7. U. S. Cancer Statistics Working Group. United States cancer statistics:1999 incidence. Atlanta, GA:Department of HeMth and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute,2002
8.盂元光,韩为东,黄柯,等.雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义[J].第四军医大学学报,2006,27(1)：980—983.
9. Mell LK, Meyer JJ, Tretiakova M, et al. Function of estrogen-related receptor alpha in human endometrial cancer[J]. Clin Cancer Res,2004,10(16):5546-5553.
10. Talvensaari-Mattila A, Santala M, Soini Y, et al. Prognostic value of matrix metalloproteinase-2 (MMP-2)expression in endometrial endometrioid adenocarcinoma [J].Anticancer Res,花2005,25(6B): 4101-4105.
11.Aglund K, Rauvala M, Puistola U, et al. Gelatinases A and B (MMP-2 and MMP-9)in endometrial cancer- MMP-9 correlates to the grade and the stage[J].Gynecol Oncol,2004,94(3):699-704.
12.尹肖云,孟元光,赵亚力,等.人类白血病相关性基因LRP16及与肿瘤关系的研究进展[J].现代肿瘤医学,2008,10(10)：1840—1843.
13.孟元光,韩为东,赵亚力,等.LRP16基因通过雌激素受体介导抑制Ishikawa细胞中E—钙黏着素的转录激活[J].生物技术通讯,2007,18(3)：368—370.
14. Meng YG, Han W D, Zhao YL, et al. Induction of LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the down regulation of E-cadherin[J]. Cell Res,2007,17(10):869-880.
15.陈美霞,孟元光,韩为东,等.LRPI6基因在子宫内膜样腺癌中的表达及意义[J].现代妇产科进展,2007,16(5)：374—377.