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20151201150151.0 |
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100428s2010 txu sbm 000 0 eng d |
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|a (OCoLC)ocn609907409
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| 035 |
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|a (OCoLC)609907409
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| 035 |
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|a (TxCM)http://hdl.handle.net/1969.1/ETD-TAMU-2433
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| 040 |
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|a TXA
|c TXA
|d UtOrBLW
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| 049 |
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|a TXAM
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| 099 |
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|a 2007
|a Dissertation
|a 1969.1/ETD-TAMU-2433
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| 100 |
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|a Wu, Fei.
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| 245 |
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|a Comparative activation of estrogen receptor alpha (er alpha) by endocrine disruptors /
|c by Fei Wu.
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| 264 |
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|a [College Station, Tex.] :
|b [Texas A&M University],
|c [2010]
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| 300 |
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|a 1 online resource.
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| 336 |
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|a text
|b txt
|2 rdacontent
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| 337 |
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|a computer
|b c
|2 rdamedia
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| 338 |
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|a online resource
|b cr
|2 rdacarrier
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| 500 |
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|a "Major Subject: Biochemistry"
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| 500 |
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|a Title from author supplied metadata (automated record created 2010-03-12 12:08:51).
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| 502 |
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|b Doctor of Philosophy
|c Texas A&M University
|d 2007
|o http://hdl.handle.net/1969.1/ETD-TAMU-2433
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| 504 |
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|a Includes bibliographical references.
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|a Text (Dissertation)
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|a Estrogen receptor a (ERa) is a ligand activated transcription factor. Many widely used synthetic compounds and natural chemicals can activate ERa. The compounds investigated in this study include 17B-estradiol (E2), diethylstilbestrol (DES), antiestrogens ICI 182,780, 4-hydroxytamoxifen, the phytoestrogen resveratrol, and the xenoestrogens bisphenol A (BPA), nonylphenol (NP), octylphenol (OP), endosulfan, kepone, 2,2-bis(p-hydroxyphenyl)-1,1,1- trichloroethane (HPTE) and 2,3,4,5-tetrachlorobiphenylol-4-ol (HO-PCB-Cl4). With the exception of the antiestrogens, all the compounds induced transactivation in MCF-7 or MDA-MB-231 cells transfected with wild-type ERa and a construct (pERE3) containing three tandem estrogen responsive elements (EREs) linked to a luciferase gene. However, these compounds differentially activated C-terminal deletion mutants of ERa. For example, neither E2 nor DES induced transactivation in MCF-7 transfected with ERa(1-537) due to partial deletion of helix 12 of ERa; however, OP, NP, resveratrol, kepone and HPTE induced this ERa mutant, demonstrating that the estrogenic activity of these synthetic compounds do not require activation function 2 (AF-2) of ERa. This study also investigated the effects of xenoestrogens on activation of reporter gene activity in MCF-7 and MDA-MB-231 cells transfected with a construct (pSp13) containing three tandem GC-rich Sp binding sites linked to the luciferase gene. In MCF-7 cells, antiestrogen-induced activation of ERa/Sp1 required the zinc finger motifs of ERa, whereas activation by estrogen and some xenoestrogens activation, such as endosulfan, NP and OP required the H12 of ERa. In contrast, xenoestrogens, such as HPTE, BPA, kepone and HO-PCBCl4, significantly induced transactivation of all four ERa deletion mutants tested in this study. Moreover, RNA interference assays demonstrated structuredependent differences in activation of ERa/Sp1, ERa/Sp3 and ERa/Sp4. The in vivo activities of E2, ICI 182,780, BPA and NP were further investigated in a transgenic mouse model containing pSp13 transgene. All the compounds induced luciferase activity in the mouse uterus; however activities observed in the penis and testis of male and stomach of both male and female mice were structure-dependent,. These results demonstrate that various ER ligands differentially activate ERa in breast cancer cells and transgenic mice, and their activities are dependent on ERa variants, promoter-, cell-context and selective use of different Sp proteins, suggesting these structurally diverse compounds are selective ER modulators (SERMs).
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| 500 |
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|a Electronic resource.
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|a Major biochemistry.
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|a endocrine disruptors
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|a breast cancer
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|a estrogen receptor
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| 700 |
1 |
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|a Safe, Stephen H.,
|e thesis advisor.
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| 856 |
4 |
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|u http://hdl.handle.net/1969.1/ETD-TAMU-2433
|z Link to OAK Trust copy
|t 0
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| 948 |
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|a cataloged
|b h
|c 2010/4/28
|d c
|e jgreene
|f 4:29:32 pm
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| 994 |
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|a C0
|b TXA
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| 999 |
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|a MARS
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|i 92ef2457-60c8-3810-9bc6-aae23c480bb3
|t 0
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| 952 |
f |
f |
|a Texas A&M University
|b College Station
|c Electronic Resources
|d Available Online
|t 0
|e 2007 Dissertation 1969.1/ETD-TAMU-2433
|h Other scheme
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| 998 |
f |
f |
|a 2007 Dissertation 1969.1/ETD-TAMU-2433
|t 0
|l Available Online
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