Estrogen Receptor β1 Inhibited Proliferation of Breast Cancer MDA-MB-231 Cell by Down-Regulating Human Telomerase Reverse Transcriptase Gene Expression_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Li , YANG Xinhua , FAN Linjun , ZHANG Yi , LIANG Yan , CHAI Fan , JIANG Jun.

Department of Breast Disease Center, The Third Military Medical University, Chongqing 400038, China;

Corresponding author：

Keywords：

Breast cancer; Estrogen receptor β1; Human telomerase reverse transcriptase; Apoptosis; Proliferation

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ObjectiveTo explore the effects of exogenous estrogen receptor β1 (ERβ1) gene on the expression of human telomerase reverse transcriptase (hTERT) as well as the changes of proliferation ability in MDA-MB-231 cell line by transfecting recombinant eukaryotic expressing vector containing ERβ1 cDNA into human breast cancer MDA-MB-231 cell. MethodsRecombinant eukaryotic expressing vector containing ERβ1 cDNA was transfected into human breast cancer MDA-MB-231 cell by using cationic liposome as transfecting agent (acted as pcDNA3.1ERβ1 transfection group), empty vector group and non-transfection group acted as controls. The expression levels in both the mRNA and protein of both the ERβ1 and hTERT were tested by real-time PCR and Western blot, respectively. The change of proliferation ability in MDA-MB-231 cell was displayed by cell growth curve, and the change of cell apoptosis was detected by flow cytometry. ResultsThe expression level of ERβ1 mRNA in the pcDNA3.1-ERβ1 transfection group (0.449±0.077) significantly increased as compared with the nontransfection group (0.153±0.035) or the empty vector group (0.160±0.020), P=0.001 or P=0.000. The expression level of ERβ1 protein in the pcDNA3.1-ERβ1 transfection group (0.847±0.065) significantly increased as compared with the non-transfection group (0.356±0.050) or the empty vector group (0.390±0.030), P=0.001 or P=0.000. The expression level of hTERT mRNA in the pcDNA3.1-ERβ1 transfection group (0.127±0.020) significantly decreased as compared with the non-transfection group (0.283±0.025) or the empty vector group (0.283±0.049), P=0.001 or P=0.002. The expression level of hTERT protein in the pcDNA3.1-ERβ1 transfection group (0.147±0.023) significantly decreased as compared with the non-transfection group (0.783±0.025) or the empty vector group (0.802±0.019), P=0.001 or P=0.002. The rate of cell apoptosis in the pcDNA3.1-ERβ1 transfection group 〔(6.15±0.94)%〕 was higher than that in the non-transfection group 〔(1.41±0.42)%〕， P=0.001. Cell proliferation curve showed that proliferation ability significantly decreased in the pcDNA3.1-ERβ1 transfected groups as compared with the non-transfection group (P lt;0.05). ConclusionERβ1 could inhibit cell growth of human breast cancer MDA-MB-231 cell by down-regulating the expression of hTERT.

Citation： CHEN Li,YANG Xinhua,FAN Linjun,ZHANG Yi,LIANG Yan,CHAI Fan,JIANG Jun.. Estrogen Receptor β1 Inhibited Proliferation of Breast Cancer MDA-MB-231 Cell by Down-Regulating Human Telomerase Reverse Transcriptase Gene Expression. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(3): 271-275. doi: Copy

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7.	Kuiper GG, Enmark E, PeltoHuikko M, et al. Cloning of a novel receptor expressed in rat prostate and ovary [J]. Proc Natl Acad Sci USA, 1996, 93(12): 59255930.
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15.	Fox EM, Davis RJ, Shupnik MA. ERbeta in breast cancer－onlooker, passive player, or active protector? [J]. Steroids, 2008, 73(11): 10391051.
16.	Chen GG, Zeng Q, Tse GM. Estrogen and its receptors in cancer [J]. Med Res Rev, 2008, 28(6): 954974.
17.	Mosselman S, Polman J, Dijkema R. ERbeta: identification and characterization of a novel human estrogen receptor [J]. FEBS Lett, 1996, 392(1): 49  53.
18.	Skliris GP, Leygue E, Watson PH, et al. Estrogen receptor alpha negative breast cancer patients: estrogen receptor beta as a therapeutic target [J]. J Steroid Biochem Mol Biol, 2008, 109(12): 110.
19.	Barker S. Nonsteroidal antiestrogens in the treatment of breast cancer [J]. Curr Opin Investig Drugs, 2006, 7(12): 10851091.
20.	Gustafsson JA, Warner M. Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer [J]. J Steroid Biochem Mol Biol, 2000, 74(5): 245248.
21.	Chen L, Qiu J H, Yang X H, et al. Identification of a novel estrogen receptor β1 binding partner, inhibitor of differentiation1, and role of ERβ1 in human breast cancer cells [J]. Cancer Lett, 2009, 278(2): 210219.
22.	陈莉, 姜军, 杨新华, 等. 乳腺癌端粒酶逆转录酶mRNA 和BRCA1蛋白表达及其相互关系 [J]. 中国普外基础与临床杂志, 2006, 13(4): 434436.
23.	Murofushi Y, Nagano S, Kamizono J, et al. Cell cyclespecific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy: a promising implication of telomerasedependent targeted cancer gene therapy [J]. Int J Oncol, 2006, 29(3): 681688.
24.	Hiyama E, Gollahon L, Kataoka T, et al. Telomerase activity in human breast tumors [J]. J Natl Cancer Inst, 1996, 88(2): 116122.

1. Hall JM, Couse JF, Korach KS. The multifaceted mechanisms of estradiol and estrogen receptor signaling [J]. J Biol Chem, 2001, 276(40): 3686936872.
2. Nilsson S, Gustafsson JA. Estrogen receptor action [J]. Crit Rev Eukaryot Gene Expr, 2002, 12(4): 237257.
3. 陈莉, 杨新华, 杨程, 等. 雌激素受体β1上调p53 基因表达促进乳腺癌细胞的凋亡 [J]. 中国普外基础与临床杂志, 2010, 17(2): 161164.
4. Kelley ST, Thackray VG. Phylogenetic analyses reveal ancient duplication of estrogen receptor isoforms [J]. J Mol Evol, 1999, 49(5): 609614.
5. Bryant DN, Dorsa DM. Roles of estrogen receptors alpha and beta in sexually dimorphic neuroprotection against glutamate toxicity [J]. Neuroscience, 2010, 170(4): 12611269.
6. Safarinejad MR, Shafiei N, Safarinejad S. Association of polymorphisms in the estrogen receptors alpha, and beta (ESR1, ESR2) with the occurrence of male infertility and semen parameters [J]. J Steroid Biochem Mol Biol, 2010, 122(4): 193203.
7. Kuiper GG, Enmark E, PeltoHuikko M, et al. Cloning of a novel receptor expressed in rat prostate and ovary [J]. Proc Natl Acad Sci USA, 1996, 93(12): 59255930.
8. Lazennec G. Estrogen receptor beta: a possible tumor suppressor involved in ovarian carcinogenesis [J]. Cancer Lett, 2006, 231(2): 151157.
9. Lo R, Matthews J. A new class of estrogen receptor betaselective activators [J]. Mol Interv, 2010, 10(3): 133136.
10. Choi JH, Min NY, Park J, et al. TSAinduced DNMT1 downregulation represses hTERT expression via recruiting CTCF into demethylated core promoter region of hTERT n HCT116 [J]. Biochem Biophys Res Commun, 2010, 391(1): 449454.
11. Liu JP, Chen W, Schwarer AP, et al. Telomerase in cancer immunotherapy [J]. Biochim Biophys Acta, 2010, 1805(1): 3542.
12. Cortez V, Mann M, Brann DW, et al. Extranuclear signaling by estrogen: role in breast cancer progression and metastasis [J]. Minerva Ginecol, 2010, 62(6): 573583.
13. Shanle EK, Xu W. Selectively targeting estrogen receptors for cancer treatment [J]. Adv Drug Deliv Rev, 2010, 62(13): 12651276.
14. Hartman J, Strm A, Gustafsson JA. Estrogen receptor beta in breast cancer-diagnostic and therapeutic implications [J]. Steroids, 2009, 74(8): 635641.
15. Fox EM, Davis RJ, Shupnik MA. ERbeta in breast cancer－onlooker, passive player, or active protector? [J]. Steroids, 2008, 73(11): 10391051.
16. Chen GG, Zeng Q, Tse GM. Estrogen and its receptors in cancer [J]. Med Res Rev, 2008, 28(6): 954974.
17. Mosselman S, Polman J, Dijkema R. ERbeta: identification and characterization of a novel human estrogen receptor [J]. FEBS Lett, 1996, 392(1): 49  53.
18. Skliris GP, Leygue E, Watson PH, et al. Estrogen receptor alpha negative breast cancer patients: estrogen receptor beta as a therapeutic target [J]. J Steroid Biochem Mol Biol, 2008, 109(12): 110.
19. Barker S. Nonsteroidal antiestrogens in the treatment of breast cancer [J]. Curr Opin Investig Drugs, 2006, 7(12): 10851091.
20. Gustafsson JA, Warner M. Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer [J]. J Steroid Biochem Mol Biol, 2000, 74(5): 245248.
21. Chen L, Qiu J H, Yang X H, et al. Identification of a novel estrogen receptor β1 binding partner, inhibitor of differentiation1, and role of ERβ1 in human breast cancer cells [J]. Cancer Lett, 2009, 278(2): 210219.
22. 陈莉, 姜军, 杨新华, 等. 乳腺癌端粒酶逆转录酶mRNA 和BRCA1蛋白表达及其相互关系 [J]. 中国普外基础与临床杂志, 2006, 13(4): 434436.
23. Murofushi Y, Nagano S, Kamizono J, et al. Cell cyclespecific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy: a promising implication of telomerasedependent targeted cancer gene therapy [J]. Int J Oncol, 2006, 29(3): 681688.
24. Hiyama E, Gollahon L, Kataoka T, et al. Telomerase activity in human breast tumors [J]. J Natl Cancer Inst, 1996, 88(2): 116122.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Estrogen Receptor β1 Inhibited Proliferation of Breast Cancer MDA-MB-231 Cell by Down-Regulating Human Telomerase Reverse Transcriptase Gene Expression

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