Estrogen Receptor β1 Induces Apoptosis of Breast Cancer by Upregulating Expression of p53 Gene_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Li , YANG Xinhua , YANG Cheng , ZHANG Lingling , REN Lin , JIANG Jun

Center of Breast Disease, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China;

Corresponding author：

Keywords：

Breast cancer; Estrogen receptor β1; p53 gene; MDA-MB-231 cell; Apoptosis

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Objective To explore the effect of exogenous estrogen receptor β1 (ERβ1) gene on the expression of p53 as well as the changes of apoptosis in MDA-MB-231 cell line and to investigate the biological role of ERβ1 in breast cancer.
Methods Recombinant eukaryotic expressing vector containing ERβ1 cDNA was transfected into human breast cancer cell MDA-MB-231 by using cationic liposome LipofectamineTM 2000. The expression levels of p53 and ERβ1 in mRNA and protein were evaluated by real-time PCR and Western blot, respectively. Cell growth curve was used to detect the changes of cell proliferation ability. Cell apoptosis was detected by flow cytometry. Results After transfected with vector containing ERβ1 cDNA, proliferation ability of MDA-MB-231 cell decreased and the expression levels of both ERβ1 and p53 in both mRNA and protein increased (P lt;0.01). Rate of cell apoptosis increased in ERβ1 upregulation groups （P lt;0.01）.
Conclusion ERβ1 can induce apoptosis and inhibit the growth of MDA-MB-231 cells by upregulating p53 expression.

Citation： CHEN Li,YANG Xinhua,YANG Cheng,ZHANG Lingling,REN Lin,JIANG Jun. Estrogen Receptor β1 Induces Apoptosis of Breast Cancer by Upregulating Expression of p53 Gene. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(2): 161-164. doi: Copy

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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.
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1. Maehle BO, Collett K, Tretli S, et al. Estrogen receptor beta-an independent prognostic marker in estrogen receptor alpha and progesterone receptorpositive breast cancer [J]. APMIS, 2009; 117(9): 644650.
2. Fox EM, Andrade J, Shupnik MA. Novel actions of estrogen to promote proliferation: integration of cytoplasmic and nuclear pathways [J]. Steroids, 2009; 74(7): 622627.
3. Hopp TA, Weiss HL, Parra IS, et al. Low levels of estrogen receptor β protein predict resistance to Tamoxifen therapy in breast cancer [J]. Clin Cancer Res, 2004; 10(22): 74907499.
4. Herynk MH, Fuqua SA. Estrogen receptors in resistance to hormone therapy [J]. Adv Exp Med Biol, 2007; 608: 130143.
5. 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, 1996; 93(12): 59255930.
6. Green CA, Peter MB, Speirs V, et al. The potential role of ER beta isoforms in the clinical management of breast cancer [J]. Histopathology, 2008; 53(4): 374380.
7. Lazennec G. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis [J]. Cancer Lett, 2006; 231(2): 151157.
8. Chen L, Qiu J, Yang X, et al. Identification of a novel estrogen receptor beta1 binding partner, inhibitor of differentiation1, and role of ERbeta1 in human breast cancer cells [J]. Cancer Lett, 2009; 278(2): 210219.
9. Matthews J, Gustafsson JA. Estrogen signaling: a subtle balance between ER alpha and ER beta [J]. Mol Interv, 2003; 3(5): 281292.
10. Cheskis BJ, Greger JG, Nagpal S, et al. Signaling by estrogens [J]. J Cell Physiol, 2007; 213(3): 610617.
11. Ji Q, Liu PI, Elshimali Y, et al. Frequent loss of estrogen and progesterone receptors in human prostatic tmmors determined by quantitative realtime PCR [J]. Mol Cell Endocrinol, 2005; 229(12): 103110.
12. Hartman J, Lindberg K, Morani A, et al. Estrogen receptor beta inhibits angiogenesis and growth of T47D breast cancer xenografts [J]. Cancer Res, 2006; 66(23): 1120711213.
13. Hartman J, Strm A, Gustafsson JA. Estrogen receptor beta in breast cancer-diagnostic and therapeutic implications [J]. Steroids, 2009; 74(8): 635641.
14. 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.
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. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40transformed cells [J]. Nature, 1979; 278(5701): 261263.
17. Meek DW. Tumour suppression by p53: a role for the DNA damage response [J]. Nat Rev Cancer, 2009; 9(10): 714723.
18. Efeyan A, Serrano M. p53: guardian of the genome and policeman of the oncogenes [J]. Cell Cycle, 2007; 6(9): 10061010.
19. Gavrieli Y, Sherman B, BenSasson SA, et al. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation [J]. J Cell Biol, 1992; 119(3): 493501.
20. Nayak SK, Panesar PS, Kumar H. p53induced apoptosis and inhibitors of p53 [J]. Curr Med Chem, 2009; 16(21): 26272640.
21. 孙治君, 周鑫, 姚榛祥，等. Pgp、nm23 和p53 联合检测判断乳腺癌预后的价值 [J]. 中国普外基础与临床杂志, 2005; 12(3): 244248.
22. Bedi A, Mookerjee B. Biological significance and molecular mechanisms of P53induced apoptosis [J]. Apoptosis, 1998; 3(4): 237244.
23. Amaral JD, Castro RE, Solá S, et al. p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis [J]. J Biol Chem, 2007; 282(47): 3425034259.
24. Hainaut P, Wiman KG. 30 years and a long way into p53 research [J]. Lancet Oncol, 2009; 10(9): 913919.
25. 于冰，孙治君. 凋亡相关基因bcl2、bax、bad与乳腺癌 [J]. 中国普外基础与临床杂志, 2007; 14(6): 739742.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Estrogen Receptor β1 Induces Apoptosis of Breast Cancer by Upregulating Expression of p53 Gene

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