Research on Expression of RASSF1A in Colonic Carcinoma Tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HE Sai ,  SUN Xuejun , ZHENG Jianbao , WANG Wei , ZHOU Peihua , WEI Guangbing , WANG Hui , YAO Jianfeng , ZHANG Li , LU Shaoying , DU Junkai

Department of General Surgery， The First Affiliated Hospital of Medical College of Xi’an Jiaotong University， Xi’an 710061， Shaanxi Province， China;

Corresponding author：

SUN Xuejun, Email: sunxy@mail.xjtu.edu.cn

Keywords：

Colonic carcinoma; RASSF1A; Immunohistochemistry; Western blot; RT-PCR

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To detect expression of Ras association domain family 1A （RASSF1A） gene in the colonic carcinoma tissue and to analyze the relationship of this expression to its clinical features.
Methods 　Immunohistochemistry and Western blot methods were employed for detecting the RASSF1A protein expressions in 34 colonic carcinoma tissues and corresponding normal colon tissues. RT-PCR was employed for detecting RASSF1A mRNA expression.
Results 　①The RASSF1A protein expression in the colonic carcinoma tissues was significantly lower than that in the normal colon
tissues by using immunohistochemistry〔35.3% （12/34） versus 97.1% （33/34）， P＜0.05〕.There were significant relati-
onships of RASSF1A protein expressions to the tumor differentiation and TNM stage （P＜0.05）， in other words， the
positive rates of RASSF1A protein in the moderately and well differentiated andⅠ＋Ⅱof TNM colonic carcinoma tissues were all higher （P＜0.05）. ② The RASSF1A protein expression in the colonic carcinoma tissues was significantly lower than that in the normal colon tissues by using Western blot 〔0.316 8±0.019 6 versus 0.914 4±0.177 6， P＜0.05〕， which
was close to the result of RT-PCR〔0.158 9±0.223 7 versus 0.572 3±0.193 9， P＜0.05〕.
Conclusions 　Absentexpre-ssion of RASSF1A gene in the colonic carcinoma tissue might play an important role in tumor genesis and tumor progre-ssion， and it might become useful early detection of the colonic carcinoma.

Citation： HE Sai,SUN Xuejun,ZHENG Jianbao,WANG Wei,ZHOU Peihua,WEI Guangbing,WANG Hui,YAO Jianfeng,ZHANG Li,LU Shaoying,DU Junkai. Research on Expression of RASSF1A in Colonic Carcinoma Tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(11): 1240-1244. doi: Copy

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6.	Guo C， Zhang X， Pfeifer GP. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2[J]. J Biol Chem， 2011， 286(8)：6253-6261.
7.	Malpeli G， Amato E， Dandrea M， et al. Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors[J]. BMC Cancer， 2011， 11：351. doi：10. 1186/1471-2407-11-351.
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9.	Jiang Y， Cui L， Chen WD， et al. The prognostic role of RASSF1Apromoter methylation in breast cancer：a meta-analysis of publisheddata[J]. PLoS One， 2012， 7(5)：e36780. doi：10. 1371/journal. pone. 0036780.
10.	杨雷，孙学军，王炜，等. MCP-1、VEGF在胃癌中的表达与幽门螺旋杆菌感染的关系[J]. 中国普外基础与临床杂志， 2009，.
11.	郑见宝，孙学军，王炜，等. HIF-1α与CDX2在结直肠腺癌组织中的表达及意义[J]. 中国普外基础与临床杂志， 2012， 17(12)：1265-1269.
12.	Zheng J， Sun X， Wang W， et al. Hypoxia-inducible factor-1alphamodulates the down-regulation of the homeodomain protein CDX2in colorectal cancer[J]. Oncol Rep， 2010， 24(1)：97-104.
13.	Wang W， Sun X， Lu L， et al. Cytotoxicity of lymphocytes activ-ated by superantigen toxic-shock-syndrome toxin-1 against colorectal cancer LoVo cells[J]. Mol Cell Biochem， 2013， 376(1-2)：.
14.	Saelee P， Wongkham S， Chariyalertsak S， et al. RASSF1A promoter hypermethylation as a prognostic marker for hepatocellular carcinoma[J]. Asian Pac J Cancer Prev， 2010， 11(6)：1677-1681.
15.	Dammann R， Li C， Yoon JH， et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour supp-ressor locus 3p21.3[J]. Nat Genet， 2000， 25(3)：315-319.
16.	Montenegro MF， Sáez-Ayala M， Piñero-Madrona A， et al. Reac-tivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation[J]. PLoS One， 2012， 7(12)：e52231. doi：10.1371/journal.pone.0052231.
17.	(5)：375-378.
18.	Park Y， Kim DS， Park KH， et al. RASSF1A and ERCC1 expre-ssion levels might be predictive of prognosis in advanced， recurrent， and metastatic squamous cell carcinoma of the head and neck treated with docetaxel and cisplatin[J]. Onkologie， 2012， 35(11)：673-682.
19.	Lin HH， Ke HL， Huang SP， et al. Increase sensitivity in detectingsuperficial， low grade bladder cancer by combination analysis of hypermethylation of E-cadherin， p16， p14， RASSF1A genes in urine[J]. Urol Oncol， 2010， 28(6)：597-602.
20.	Martins AT， Monteiro P， Ramalho-Carvalho J， et al. High RASSF1A promoter methylation levels are predictive of poor prog-nosis in fine-needle aspirate washings of breast cancer lesions[J]. Breast Cancer Res Treat， 2011， 129(1)：1-9.
21.	Ghazaleh HA， Chow RS， Choo SL， et al. 14-3-3 mediated regulation of the tumor suppressor protein， RASSF1A[J]. Apoptosis，.
22.	Richter AM， Pfeifer GP， Dammann RH. The RASSF proteins in cancer；from epigenetic silencing to functional characterization[J]. Biochim Biophys Acta， 2009， 1796(2)：114-128.
23.	顾全凯，闫庆辉，王凤安，等. TIMP-3和RASSF1A在大肠癌中的表达及临床意义[J]. 世界华人消化杂志， 2012， 20(27)：2642-2647.
24.	Thaler S， Hähnel PS， Schad A， et al. RASSF1A mediates p21Cip1/Waf1-dependent cell cycle arrest and senescence through modulation of the Raf-MEK-ERK pathway and inhibition of Akt[J]. Cancer Res， 2009， 69(5)：1748-1757.
25.	Gordon M， Baksh S. RASSF1A：Not a prototypical Ras effector[J]. Small GTPases， 2011， 2(3)：148-157.
26.	， 15(2)：117-127.

1. László L. Predictive and prognostic factors in the complex treatment of patients with colorectal cancer[J]. Magy Onkol， 2010， 54(4)：383-394.
2. -9.
3. Xiang TX， Yuan Y， Li LL， et al. Aberrant promoter CpG methyl-ation and its translational applications in breast cancer[J]. Chin J Cancer， 2013， 32(1)：12-20.
4. Van der Weyden L， Papaspyropoulos A， Poulogiannis G， et al. Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis[J]. Cancer Res， 2012， 72(15)：3817-3827.
5. Sherwood V， Recino A， Jeffries A， et al. The N-terminal RASSF family：a new group of Ras-association-domain-containing proteins，with emerging links to cancer formation[J]. Biochem J， 2010， 425(2)：303-311.
6. Guo C， Zhang X， Pfeifer GP. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2[J]. J Biol Chem， 2011， 286(8)：6253-6261.
7. Malpeli G， Amato E， Dandrea M， et al. Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors[J]. BMC Cancer， 2011， 11：351. doi：10. 1186/1471-2407-11-351.
8. Tian Y， Hou Y， Zhou X， et al. Tumor suppressor RASSF1A promoter：p53 binding and methylation[J]. PLoS One， 2011， 6(2)：e17017. doi：10.1371/journal.pone.0017017.
9. Jiang Y， Cui L， Chen WD， et al. The prognostic role of RASSF1Apromoter methylation in breast cancer：a meta-analysis of publisheddata[J]. PLoS One， 2012， 7(5)：e36780. doi：10. 1371/journal. pone. 0036780.
10. 杨雷，孙学军，王炜，等. MCP-1、VEGF在胃癌中的表达与幽门螺旋杆菌感染的关系[J]. 中国普外基础与临床杂志， 2009，.
11. 郑见宝，孙学军，王炜，等. HIF-1α与CDX2在结直肠腺癌组织中的表达及意义[J]. 中国普外基础与临床杂志， 2012， 17(12)：1265-1269.
12. Zheng J， Sun X， Wang W， et al. Hypoxia-inducible factor-1alphamodulates the down-regulation of the homeodomain protein CDX2in colorectal cancer[J]. Oncol Rep， 2010， 24(1)：97-104.
13. Wang W， Sun X， Lu L， et al. Cytotoxicity of lymphocytes activ-ated by superantigen toxic-shock-syndrome toxin-1 against colorectal cancer LoVo cells[J]. Mol Cell Biochem， 2013， 376(1-2)：.
14. Saelee P， Wongkham S， Chariyalertsak S， et al. RASSF1A promoter hypermethylation as a prognostic marker for hepatocellular carcinoma[J]. Asian Pac J Cancer Prev， 2010， 11(6)：1677-1681.
15. Dammann R， Li C， Yoon JH， et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour supp-ressor locus 3p21.3[J]. Nat Genet， 2000， 25(3)：315-319.
16. Montenegro MF， Sáez-Ayala M， Piñero-Madrona A， et al. Reac-tivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation[J]. PLoS One， 2012， 7(12)：e52231. doi：10.1371/journal.pone.0052231.
17. (5)：375-378.
18. Park Y， Kim DS， Park KH， et al. RASSF1A and ERCC1 expre-ssion levels might be predictive of prognosis in advanced， recurrent， and metastatic squamous cell carcinoma of the head and neck treated with docetaxel and cisplatin[J]. Onkologie， 2012， 35(11)：673-682.
19. Lin HH， Ke HL， Huang SP， et al. Increase sensitivity in detectingsuperficial， low grade bladder cancer by combination analysis of hypermethylation of E-cadherin， p16， p14， RASSF1A genes in urine[J]. Urol Oncol， 2010， 28(6)：597-602.
20. Martins AT， Monteiro P， Ramalho-Carvalho J， et al. High RASSF1A promoter methylation levels are predictive of poor prog-nosis in fine-needle aspirate washings of breast cancer lesions[J]. Breast Cancer Res Treat， 2011， 129(1)：1-9.
21. Ghazaleh HA， Chow RS， Choo SL， et al. 14-3-3 mediated regulation of the tumor suppressor protein， RASSF1A[J]. Apoptosis，.
22. Richter AM， Pfeifer GP， Dammann RH. The RASSF proteins in cancer；from epigenetic silencing to functional characterization[J]. Biochim Biophys Acta， 2009， 1796(2)：114-128.
23. 顾全凯，闫庆辉，王凤安，等. TIMP-3和RASSF1A在大肠癌中的表达及临床意义[J]. 世界华人消化杂志， 2012， 20(27)：2642-2647.
24. Thaler S， Hähnel PS， Schad A， et al. RASSF1A mediates p21Cip1/Waf1-dependent cell cycle arrest and senescence through modulation of the Raf-MEK-ERK pathway and inhibition of Akt[J]. Cancer Res， 2009， 69(5)：1748-1757.
25. Gordon M， Baksh S. RASSF1A：Not a prototypical Ras effector[J]. Small GTPases， 2011， 2(3)：148-157.
26. ， 15(2)：117-127.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research on Expression of RASSF1A in Colonic Carcinoma Tissues

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