• 第三軍醫(yī)大學(xué)附屬西南醫(yī)院乳腺中心（重慶400038）;

目的  觀察外源性雌激素受體β1（estrogen receptor β1，ERβ1）基因轉(zhuǎn)染乳腺癌MDA-MB-231細(xì)胞后對(duì)p53基因表達(dá)和細(xì)胞凋亡的影響，探討ERβ1在乳腺癌中的生物學(xué)作用。
方法  應(yīng)用脂質(zhì)體法將ERβ1真核表達(dá)質(zhì)粒轉(zhuǎn)染至乳腺癌MDA-MB-231細(xì)胞中，分別用熒光實(shí)時(shí)定量PCR法、Western blot法檢測(cè)轉(zhuǎn)染前、后細(xì)胞中ERβ1與p53 mRNA和蛋白表達(dá)的變化，流式細(xì)胞儀檢測(cè)細(xì)胞凋亡率。細(xì)胞生長曲線顯示轉(zhuǎn)染前、后細(xì)胞增殖能力的改變。
結(jié)果  轉(zhuǎn)染外源性ERβ1真核表達(dá)質(zhì)粒后，MDA-MB-231細(xì)胞中ERβ1及p53 mRNA和蛋白表達(dá)明顯增強(qiáng)（P lt;0.01）; 細(xì)胞凋亡率明顯增加（P lt;0.01），增殖能力明顯減弱（P lt;0.01）。
結(jié)論  在乳腺癌中，ERβ1可以通過上調(diào)p53基因表達(dá)促進(jìn)乳腺癌細(xì)胞凋亡，從而抑制乳腺癌細(xì)胞的增殖。

引用本文： 陳莉,楊新華,楊程,張玲玲,任林,姜軍. 雌激素受體β1上調(diào)p53基因表達(dá)促進(jìn)乳腺癌細(xì)胞的凋亡. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(2): 161-164. doi: 復(fù)制

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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. 孫治君, 周鑫, 姚榛祥， 等. Pgp、nm23 和p53 聯(lián)合檢測(cè)判斷乳腺癌預(yù)后的價(jià)值 [J]. 中國普外基礎(chǔ)與臨床雜志, 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， 孫治君. 凋亡相關(guān)基因bcl2、bax、bad與乳腺癌 [J]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14(6): 739742.
  1. 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. 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. 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. 4. Herynk MH, Fuqua SA. Estrogen receptors in resistance to hormone therapy [J]. Adv Exp Med Biol, 2007; 608: 130143.
  5. 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. 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. 7. Lazennec G. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis [J]. Cancer Lett, 2006; 231(2): 151157.
  8. 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. 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. 10. Cheskis BJ, Greger JG, Nagpal S, et al. Signaling by estrogens [J]. J Cell Physiol, 2007; 213(3): 610617.
  11. 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. 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. 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. 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. 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. 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. 17. Meek DW. Tumour suppression by p53: a role for the DNA damage response [J]. Nat Rev Cancer, 2009; 9(10): 714723.
  18. 18. Efeyan A, Serrano M. p53: guardian of the genome and policeman of the oncogenes [J]. Cell Cycle, 2007; 6(9): 10061010.
  19. 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. 20. Nayak SK, Panesar PS, Kumar H. p53induced apoptosis and inhibitors of p53 [J]. Curr Med Chem, 2009; 16(21): 26272640.
  21. 21. 孫治君, 周鑫, 姚榛祥， 等. Pgp、nm23 和p53 聯(lián)合檢測(cè)判斷乳腺癌預(yù)后的價(jià)值 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(3): 244248.
  22. 22. Bedi A, Mookerjee B. Biological significance and molecular mechanisms of P53induced apoptosis [J]. Apoptosis, 1998; 3(4): 237244.
  23. 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. 24. Hainaut P, Wiman KG. 30 years and a long way into p53 research [J]. Lancet Oncol, 2009; 10(9): 913919.
  25. 25. 于冰， 孫治君. 凋亡相關(guān)基因bcl2、bax、bad與乳腺癌 [J]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14(6): 739742.