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研究生：	李蕙萍 Lee, Hui-Ping
論文名稱：	利用免疫沉澱和鑑別性的蛋白質譜分析研究由雌激素受體-β參與HeLa之細胞增生 Immunoprecipitation coupled with differential proteomic analysis to study the involvement of estrogen receptor β in HeLa cell proliferation
指導教授：	蔡美玲 Tsai, Mei-Ling
學位類別：	碩士 Master
系所名稱：	醫學院 - 生理學研究所 Department of Physiology
論文出版年：	2010
畢業學年度：	98
語文別：	英文
論文頁數：	80
中文關鍵詞：	雌激素、蛋白質體
外文關鍵詞：	estrogen, proteomic
相關次數：	點閱：95 下載：1
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子宮頸癌是世界女性第二普遍發生的癌症。雖然人類乳突病毒是導致子宮頸癌主要的因子，但其他因子如雌性激素，也被認為會參與子宮頸癌的形成。雌性激素有兩種雌激素受體 (ERα和ERβ)，目前大部分與雌性激素相關之研究是在乳癌上。目前在乳癌上已知活化的ERα 經由基因組和非基因組途徑增加細胞增生；活化的ERβ主要經由非基因組途徑利用修飾ERα的活性而降低細胞增生與增加細胞凋亡。另外也知道ERα參與子宮頸癌的細胞增生，但是較少的報告探究在子宮頸癌中ERβ在細胞增生的角色，所以此論文的目的是要在子宮頸癌細胞株HeLa中發現活化的ERβ調控細胞增生的非基因組機制。首先偵測乳腺細胞 (4T1和MCF7) 、肺細胞(A549和L2)及子宮頸癌細胞HeLa，其ERα和ERβ的表現量。與表現ERα和ERβ的MCF7相比，A549、L2、HeLa和4T1只表現ERβ。MTT分析顯示雌激素增加MCF7的生存能力，降低HeLa的生存能力。1μM的雌激素在MCF7中降低G0/G1和增加S時期的細胞，進而使細胞數增加。但在HeLa中增加Sub G0和降低S時期的細胞進而導致細胞數下降。過度表現ERβ在MCF7中增加Sub G0期的細胞，並降低S和G2/M時期的細胞。但在HeLa中不影響Sub G0期的細胞，只降低S和G2/M時期的細胞。免疫沉澱和鑑別性的蛋白質譜分析顯示：1 μM雌激素降低與ERβ連接之蛋白比例包含了組蛋白H4, 甲狀腺受體連接蛋白和熱休克蛋白90 (Hsp90)，並增加了核內組蛋白H2B及H1.2的比例。然而，10 nM的雌性激素降低核內組蛋白H2B的含量，且增加proliferation associated-protein 2G4。我們的發現顯示在HeLa細胞株中，1 μM雌激素和ERβ結合之後，會導致ERβ與組蛋白H4及Hsp90分離，而可能參與了細胞週期進入S和G2/M時期的減慢最後導致細胞數減少。另外，發現10 nM雌性激素不影響HeLa細胞株的細胞週期。

Cervical cancer is the second most common cancer among women worldwide. Although high risk human papillomavirus (HPV) is the major factor for cervical cancer, other factors such as E2, a major estrogen, are thought to play roles in the formation of cervical cancer. E2 has two types of estrogen receptors (ERα and ERβ), and most estrogen-related studies are in breast cancer. It was known that activated ERα increases cell proliferation through both genomic and non-genomic pathways; activated ERβ decreases cell proliferation and increases apoptosis by modulating ERα activity, mainly through non-genomic pathways in breast cancer cells. The ERα is also required for proliferation in cervical cancer. However, there are fewer reports explore the role of ERβ in cell proliferation in cervical cancer cells. The purpose of this study was to discover the non-genomic mechanism by which activated ERβ modulated cell proliferation in HeLa cells, a cervical cancer cell line. First of all, the expression of ERα and ERβ in mammary gland cells (4T1 and MCF7), lung cells (A549 and L2) and a cervical cancer cell (HeLa) was detected. When compared with MCF7 which expressed ERα and ERβ, A549, L2, HeLa and 4T1 expressed ERβ only. MTT assay showed that E2 at 1 μM increased the viability of MCF7, and decreased viability of HeLa. E2 at 1 μM increased cell number in conjunction with the decrease cells at G0/G1 and increased cells at S in MCF7 but that decreased cell number in conjunction with the increased cells at Sub G0 and the decreased cells at S in HeLa. Overexpression of ERβincreased the cells at Sub G0 and decreased the cells at S and G2/M in MCF7 but that did not affect the cells at Sub G0 and decreased the cells at S and G2/M in HeLa. Immunoprecipitation coupled with differential proteomic analysis showed E2 (at 1 μM)-mediated decreases in the abundance ratio of proteins associated with ERβ, including histone H4, thyroid hormone receptor-associated protein, and heat shock protein 90 (Hsp90), and increased the abundance of histone H2B and H1.2 in the nuclei. However, E2 at 10 nM decreased the histone H2B and increased proliferation associated-protein 2G4 in the nuclei. All our findings suggest that the binding of E2 at 1 μM to ERβ causes the dissociation of histone H4 and Hsp90 from the ERβ complex, which may contribute to the deceleration of cell cycle progression to S and G2/M phases and decrease cell number in HeLa cells. And E2 at 10 nM did not affect cell cycle progression in HeLa cells.

Contents
中文摘要	i
Abstract	ii
誌謝	iii
Contents	iv
List of Tables	vii
List of Figures	viii
Chapter 1: Introduction	1
I.	Physiological roles of E2 in female reproductive organs	1
1.	Functional roles of E2 in menstrual cycles	1
2.	The roles of E2 in cervical cycles	2
3.	The roles of E2 in breast development	2
II.	Occurrence of cervical cancer in women world	3
1.	Epidemiological studies of cervical cancer	3
2.	The anatomy of cervix	3
3.	Risk factors of cervical cancer	4
III.	Molecular mechanism of E2-mediated cell proliferation in breast epithelial cells	5
1.	Genomic pathways- ER-ERE-dependent pathway	5
2.	Genomic pathways- ER-ERE-independent pathway	6
3.	Non-genomic pathways: ER-dependent pathways	6
IV.	The effects of ERα and ERβ on the progression of cell cycle in breast epithelial cells	7
1.	Biochemical properties of ERα and ERβ	7
2.	Estrogen-dependent regulation on the proliferation of breast cancer cells	8
3.	The role of ERα in cell proliferation through both genomic and non-genomic pathways	10
4.	The role of ERβ in cell proliferation through genomic and non-genomic pathways	11
V.	The purpose of this study	11
1.	Current studies of E2 on cell proliferation in cervical epithelium	………………………………………………………………….11
2.	Hypothesis	12
Chapter 2: Materials and Methods	14
I.	Cell culture	14
1.	Cell line and culture	14
2.	Treatment protocol	14
II.	Sample preparation	15
1.	Cell lysate	15
2.	Subcellular fractionation	15
3.	Extration of crude nuclear proteins	16
4.	Immunoprecipitation	16
5.	Transfection of ERb plasmid into HeLa cells	17
III.	Analysis of cell viability and proliferation	18
1.	Western blot analysis	18
2.	MTT assay	19
3.	Cell counting assay	19
4.	Analysis of cell cycle by flow cytometry	20
IV.	Proteomic analysis	20
1.	Solution digestion	20
2.	Stable isotope dimethyl labeling	21
3.	LC-MS/MS system	21
4.	Quantitative analysis and functional annotation of dimethyl labeled peptides	23
V.	Data analysis and statistics	23
Chapter 3: Results	25
Objective 1: The effects of E2 on cell viability in various cells	25
Objective 2: The effects of E2 on cell cycle progression in HeLa cells	25
Objective 3: The effects of ERβ overexpression on cell cycle progression in HeLa cells	26
Objective 4: To investigate new pathways of ERβ on the reduction of cell proliferation in HeLa cells after the treatment of E2 at 1 μM	27
Objective 5: To confirm the association of proteins with ERβ is E2-dependent	28
Objective 6: To analyze large-scale proteins were modulated by activated-ERβ	29
Objective 7: To confirm the ERβ-mediated action is E2-dependent	30
Chapter 4: Discussion	31
References:	36
Curriculum Vitae	80
 
List of Tables
Table 1. A list of primary and secondary antibodies used in this study	42
Table 2. Parameters for database search	43
Table 3. Quantitative proteome of ERβ-associated proteins under 1 μM E2 treatment in HeLa cells	44
Table 4. Quantitative proteome of ERβ-associated proteins under 10 nM E2 treatment in HeLa cells	47
Table 5. Quantitative proteome of nuclear proteins under 1 μM E2 treatment in HeLa cells	49
Table 6. Quantitative proteome of nuclear proteins under 10 nM E2 treatment in HeLa cells	51
Table 7. A list of E2 at 1 μM altered proteins with ratio > 1.2 or ratio < 0.8 in HeLa cells	54
Table 8. A list of E2 at 10 nM altered proteins with ratio > 1.2 or ratio < 0.8 in HeLa cells	55
 
List of Figures
Figure 1. ERβ expression in various whole cell lysates.	56
Figure 2. The effects of E2 on cell viability in HeLa.	57
Figure 3. The dose effects of E2 on cell numbers in MCF7 and HeLa.	58
Figure 4. Dose-effects of E2 on cell cycle in MCF7.	59
Figure 5. Dose-effects of E2 on cell cycle in HeLa.	60
Figure 6. Transient transfection efficiency of ERβ in HeLa and MCF7.	61
Figure 7. Dose-effects of E2 on cell cycle in ERβ-overexpressed MCF7.	62
Figure 8. Dose-effects of E2 on cell cycle in ERβ-overexpressed HeLa.	63
Figure 9. The flowchart of immunoprecipitation coupled with quantitative proteomics.	64
Figure 10. Functional annotation of quantified proteome of ERb-associated proteins under 1 μM E2 treatment in HeLa cells by ExPASy Proteomics Server.	65
Figure 11. The relative abundance of quantified proteins which associated with ERβ under 1 μM E2 treatment in HeLa cells.	66
Figure 12. Validation of ERβ-associated proteins.	68
Figure 13. Functional annotation of quantified proteome of ERb-associated proteins under 10 nM E2 treatment in HeLa cells by ExPASy Proteomics Server.	69
Figure 14. The relative abundance of quantified proteins which associated with ERβ under 10 nM E2 treatment in HeLa cells.	70
Figure 15. Functional annotation of quantified proteome of ERb-modulated proteins under 1 μM E2 treatment in HeLa cells by ExPASy Proteomics Server.	71
Figure 16. The relative abundance of quantified proteins which modulated by activated-ERβ under 1 μM E2 treatment in HeLa cells.	72
Figure 17. Functional annotation of quantified proteome of ERb-modulated proteins under 10 nM E2 treatment in HeLa cells by ExPASy Proteomics Server.	73
Figure 18. The relative abundance of quantified proteins which modulated by activated-ERβ under 10 nM E2 treatment in HeLa cells.	74
Figure 19. The possible mechanism of activated ERβ on cell cycle progression under 1 μM E2 treatment.	75
Figure 20. The possible mechanism of activated ERβ on cell cycle progression under 10 nM E2treatment.	76
Figure A 1. The dose effects of charcoal-stripped-FBS (DCC-FBS) for 96 hr on cell cycle in HeLa.	77
Figure A 2. The dose effects of charcoal-stripped-FBS for 24 hr on cell cycle in HeLa.	78
Figure A 3. The dose effects of charcoal-stripped-FBS for 24 hr on cell cycle in HeLa.	79


                                    

1. Widmaier E, Raff H, Strang K. Vander's human physiology. The mechanisms of body function. 10th edition; 2006.
2. Gorodeski G. The cervical cycle. New York: Lippincott-Raven; 1996.
3. Lamote I, Meyer E, Massart-Leen AM, Burvenich C. Sex steroids and growth factors in the regulation of mammary gland proliferation, differentiation, and involution. Steroids 2004; 69: 145-59.
4. Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006; 20: 207-25.
5. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37 Suppl 8: S4-66.
6. Minamoto T, Arai K, Hirakawa S, Nagai Y. Immunohistochemical studies on collagen types in the uterine cervix in pregnant and nonpregnant states. Am J Obstet Gynecol 1987; 156: 138-44.
7. Ehrmann RL. Benign to malignant progression in cervical squamous epithelium. New York Igaku-Shoin; 1994.
8. Fu YS, Reagan JW. Pathology of the uterine cervix, vagina, and vulva. 1989.
9. Stern PL, Stanley MA. Human papillomaviruses and cervical cancer :biology and immunology. 1994.
10. Forsberg JG. Cervicovaginal epithelium: its origin and development. Am J Obstet Gynecol 1973; 115: 1025-43.
11. Jenkins D. Histopathology and cytopathology of cervical cancer. Dis Markers 2007; 23: 199-212.
12. Waggoner SE. Cervical cancer. Lancet 2003; 361: 2217-25.
13. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003; 16: 1-17.
14. Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003; 361: 1159-67.
15. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007; 370: 890-907.
16. Kim CJ, Um SJ, Kim TY, et al. Regulation of cell growth and HPV genes by exogenous estrogen in cervical cancer cells. Int J Gynecol Cancer 2000; 10: 157-64.
17. Wang Q, Li X, Wang L, Feng YH, Zeng R, Gorodeski G. Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells. Endocrinology 2004; 145: 5568-79.
18. Lorenzo J. A new hypothesis for how sex steroid hormones regulate bone mass. J Clin Invest 2003; 111: 1641-3.
19. Nilsson S, Makela S, Treuter E, et al. Mechanisms of estrogen action. Physiol Rev 2001; 81: 1535-65.
20. Collins P, Webb C. Estrogen hits the surface. Nat Med 1999; 5: 1130-1.
21. Prossnitz ER, Arterburn JB, Sklar LA. GPR30: A G protein-coupled receptor for estrogen. Mol Cell Endocrinol 2007; 265-266: 138-42.
22. Filardo EJ, Quinn JA, Frackelton AR, Jr., Bland KI. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol 2002; 16: 70-84.
23. Weihua Z, Andersson S, Cheng G, Simpson ER, Warner M, Gustafsson JA. Update on estrogen signaling. FEBS Lett 2003; 546: 17-24.
24. Green S, Kumar V, Krust A, Walter P, Chambon P. Structural and functional domains of the estrogen receptor. Cold Spring Harb Symp Quant Biol 1986; 51 Pt 2: 751-8.
25. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996; 93: 5925-30.
26. Saji S, Hirose M, Toi M. Clinical significance of estrogen receptor beta in breast cancer. Cancer Chemother Pharmacol 2005; 56 Suppl 1: 21-6.
27. Schafer KA. The cell cycle: a review. Vet Pathol 1998; 35: 461-78.
28. Bonenfant D, Towbin H, Coulot M, Schindler P, Mueller DR, van Oostrum J. Analysis of dynamic changes in post-translational modifications of human histones during cell cycle by mass spectrometry. Mol Cell Proteomics 2007; 6: 1917-32.
29. Rusan NM, Peifer M. A role for a novel centrosome cycle in asymmetric cell division. J Cell Biol 2007; 177: 13-20.
30. Ceballos E, Munoz-Alonso MJ, Berwanger B, et al. Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes. Oncogene 2005; 24: 4559-71.
31. Freytag SO. Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G0/G1. Mol Cell Biol 1988; 8: 1614-24.
32. Mauleon I, Lombard MN, Munoz-Alonso MJ, Canelles M, Leon J. Kinetics of myc-max-mad gene expression during hepatocyte proliferation in vivo: Differential regulation of mad family and stress-mediated induction of c-myc. Mol Carcinog 2004; 39: 85-90.
33. Munoz-Alonso MJ, Acosta JC, Richard C, Delgado MD, Sedivy J, Leon J. p21Cip1 and p27Kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells. J Biol Chem 2005; 280: 18120-9.
34. Wu S, Cetinkaya C, Munoz-Alonso MJ, et al. Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 2003; 22: 351-60.
35. Kaiser BK, Zimmerman ZA, Charbonneau H, Jackson PK. Disruption of centrosome structure, chromosome segregation, and cytokinesis by misexpression of human Cdc14A phosphatase. Mol Biol Cell 2002; 13: 2289-300.
36. Ou Y, Rattner JB. The centrosome in higher organisms: structure, composition, and duplication. Int Rev Cytol 2004; 238: 119-82.
37. Azimzadeh J, Bornens M. Structure and duplication of the centrosome. J Cell Sci 2007; 120: 2139-42.
38. Seong YS, Kamijo K, Lee JS, et al. A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells. J Biol Chem 2002; 277: 32282-93.
39. Comin-Anduix B, Agell N, Bachs O, Ovadi J, Cascante M. A new bis-indole, KARs, induces selective M arrest with specific spindle aberration in neuroblastoma cell line SH-SY5Y. Mol Pharmacol 2001; 60: 1235-42.
40. Wu ZZ, Chien CM, Yang SH, et al. Induction of G2/M phase arrest and apoptosis by a novel enediyne derivative, THDA, in chronic myeloid leukemia (K562) cells. Mol Cell Biochem 2006; 292: 99-105.
41. Wang W, Dong L, Saville B, Safe S. Transcriptional activation of E2F1 gene expression by 17beta-estradiol in MCF-7 cells is regulated by NF-Y-Sp1/estrogen receptor interactions. Mol Endocrinol 1999; 13: 1373-87.
42. Wang W, Smith R, 3rd, Safe S. Aryl hydrocarbon receptor-mediated antiestrogenicity in MCF-7 cells: modulation of hormone-induced cell cycle enzymes. Arch Biochem Biophys 1998; 356: 239-48.
43. Planas-Silva MD, Weinberg RA. Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution. Mol Cell Biol 1997; 17: 4059-69.
44. Foster JS, Wimalasena J. Estrogen regulates activity of cyclin-dependent kinases and retinoblastoma protein phosphorylation in breast cancer cells. Mol Endocrinol 1996; 10: 488-98.
45. Prall OW, Sarcevic B, Musgrove EA, Watts CK, Sutherland RL. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem 1997; 272: 10882-94.
46. Wiebe JP. Progesterone metabolites in breast cancer. Endocr Relat Cancer 2006; 13: 717-38.
47. O'Lone R, Frith MC, Karlsson EK, Hansen U. Genomic targets of nuclear estrogen receptors. Mol Endocrinol 2004; 18: 1859-75.
48. Castoria G, Migliaccio A, Bilancio A, et al. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J 2001; 20: 6050-9.
49. Song RX, Fan P, Yue W, Chen Y, Santen RJ. Role of receptor complexes in the extranuclear actions of estrogen receptor alpha in breast cancer. Endocr Relat Cancer 2006; 13 Suppl 1: S3-13.
50. Saville B, Wormke M, Wang F, et al. Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements. J Biol Chem 2000; 275: 5379-87.
51. Strom A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson JA. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci U S A 2004; 101: 1566-71.
52. Helguero LA, Faulds MH, Gustafsson JA, Haldosen LA. Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene 2005; 24: 6605-16.
53. Arbeit JM, Howley PM, Hanahan D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci U S A 1996; 93: 2930-5.
54. Nair HB, Luthra R, Kirma N, et al. Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Cancer Res 2005; 65: 11164-73.
55. Chung SH, Wiedmeyer K, Shai A, Korach KS, Lambert PF. Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer. Cancer Res 2008; 68: 9928-34.
56. Cox B, Emili A. Tissue subcellular fractionation and protein extraction for use in mass-spectrometry-based proteomics. Nat Protoc 2006; 1: 1872-8.
57. Vitorino R, Ferreira R, Neuparth M, et al. Subcellular proteomics of mice gastrocnemius and soleus muscles. Anal Biochem 2007; 366: 156-69.
58. Guillemin I, Becker M, Ociepka K, Friauf E, Nothwang HG. A subcellular prefractionation protocol for minute amounts of mammalian cell cultures and tissue. Proteomics 2005; 5: 35-45.
59. Tang MJ, Hu JJ, Lin HH, Chiu WT, Jiang ST. Collagen gel overlay induces apoptosis of polarized cells in cultures: disoriented cell death. Am J Physiol 1998; 275: C921-31.
60. Catts VS, Catts SV, McGrath JJ, et al. Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines. Schizophr Res 2006; 84: 20-8.
61. Mollerup S, Jorgensen K, Berge G, Haugen A. Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer 2002; 37: 153-9.
62. Stabile LP, Davis AL, Gubish CT, et al. Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res 2002; 62: 2141-50.
63. Hershberger PA, Vasquez AC, Kanterewicz B, Land S, Siegfried JM, Nichols M. Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands. Cancer Res 2005; 65: 1598-605.
64. Berry NB, Fan M, Nephew KP. Estrogen receptor-alpha hinge-region lysines 302 and 303 regulate receptor degradation by the proteasome. Mol Endocrinol 2008; 22: 1535-51.
65. Ford CE, Ekstrom EJ, Andersson T. Wnt-5a signaling restores tamoxifen sensitivity in estrogen receptor-negative breast cancer cells. Proc Natl Acad Sci U S A 2009; 106: 3919-24.
66. Guo JM, Kang GZ, Xiao BX, Liu DH, Zhang S. Effect of daidzein on cell growth, cell cycle, and telomerase activity of human cervical cancer in vitro. Int J Gynecol Cancer 2004; 14: 882-8.
67. Zhang B, Liu JY, Pan JS, et al. Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells. J Pharmacol Sci 2006; 102: 129-35.
68. Horner-Glister E, Maleki-Dizaji M, Guerin CJ, Johnson SM, Styles J, White IN. Influence of oestradiol and tamoxifen on oestrogen receptors-alpha and -beta protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells. J Mol Endocrinol 2005; 35: 421-32.
69. Sundar SN, Marconett CN, Doan VB, Willoughby JA, Sr., Firestone GL. Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells. Carcinogenesis 2008; 29: 2252-8.
70. Hodges-Gallagher L, Valentine CD, El Bader S, Kushner PJ. Estrogen receptor beta increases the efficacy of antiestrogens by effects on apoptosis and cell cycling in breast cancer cells. Breast Cancer Res Treat 2008; 109: 241-50.
71. Omoto Y, Eguchi H, Yamamoto-Yamaguchi Y, Hayashi S. Estrogen receptor (ER) beta1 and ERbetacx/beta2 inhibit ERalpha function differently in breast cancer cell line MCF7. Oncogene 2003; 22: 5011-20.
72. Behrens D, Gill JH, Fichtner I. Loss of tumourigenicity of stably ERbeta-transfected MCF-7 breast cancer cells. Mol Cell Endocrinol 2007; 274: 19-29.
73. Ganong WF. Review of medical phsiology. 18th edition; 1997.
74. Khodarev NN, Narayana A, Constantinou A, Vaughan AT. Topologically constrained domains of supercoiled DNA in eukaryotic cells. DNA Cell Biol 1997; 16: 1051-8.
75. Svotelis A, Gevry N, Gaudreau L. Regulation of gene expression and cellular proliferation by histone H2A.Z. Biochem Cell Biol 2009; 87: 179-88.
76. Henikoff S, Furuyama T, Ahmad K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet 2004; 20: 320-6.
77. Dhillon N, Oki M, Szyjka SJ, Aparicio OM, Kamakaka RT. H2A.Z functions to regulate progression through the cell cycle. Mol Cell Biol 2006; 26: 489-501.
78. Altaf M, Auger A, Covic M, Cote J. Connection between histone H2A variants and chromatin remodeling complexes. Biochem Cell Biol 2009; 87: 35-50.
79. Bosch A, Suau P. Changes in core histone variant composition in differentiating neurons: the roles of differential turnover and synthesis rates. Eur J Cell Biol 1995; 68: 220-5.
80. Govin J, Caron C, Rousseaux S, Khochbin S. Testis-specific histone H3 expression in somatic cells. Trends Biochem Sci 2005; 30: 357-9.
81. Tachiwana H, Osakabe A, Kimura H, Kurumizaka H. Nucleosome formation with the testis-specific histone H3 variant, H3t, by human nucleosome assembly proteins in vitro. Nucleic Acids Res 2008; 36: 2208-18.

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