Interaction of 2,3,7,8-Tetrachlorodibenzo-p-dioxin with other signal transduction pathways in human breast cancer cells /
In MCF-7 cells treated with 2,3,7,8-Tetrachlorodibenzo-p- dioxin (TCDD), 12-0tetradecanoylphorbol- 13 -acetate (TPA) causes a time- and concentration-dependent modulation of TCDD-induced CYP 1 AI gene expression. At 0. 1 ng/ml, TPA blocks the inhibitory effects of TCDD on estrogen-induced metabolis...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1995.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=742744981&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | In MCF-7 cells treated with 2,3,7,8-Tetrachlorodibenzo-p- dioxin (TCDD), 12-0tetradecanoylphorbol- 13 -acetate (TPA) causes a time- and concentration-dependent modulation of TCDD-induced CYP 1 AI gene expression. At 0. 1 ng/ml, TPA blocks the inhibitory effects of TCDD on estrogen-induced metabolism of glucose; however, TPA did not affect the inhibition of estrogen-induced procathepsin D levels by TCDD. In addition, the low dose of TPA only caused a minimal decrease in TCDD-induced EROD activity. In contrast, cotreatment of MCF-7 cells with higher concentrations of TPA (1.0 to 100 ng/ml) significantly modulated TCDD-induced EROD activity. After exposure to TPA for 26 to 30 h, TCDD-induced EROD activity and CYPIAI MRNA levels were significantlv reduced. Surprisingly, there was a 2- to 3-fold increase in the induced CYP IAI gene expression in MCF-7 cells treated for 72 to 96 h. The biphasic temporal effects of TPA on TCDD induced CYPIAI gene expression in MCF-7 cells were paralleled by comparable changes in nuclear AhR levels and binding to a synthetic DRE increase in nuclear AhR levels and nuclear AHR- DRE complexes. Benzo[a]pyrene resistant (BapR) MCF-7 and T47D cells were isolated and Ah-responsiveness was investigated. TCDD induced CYP IA I gene expression and inhibited selected estrogen-induced responses in wild-type but not BapR MCF-7 cells. The loss of Ah-responsiveness in the BapR MCF-7 cells correlated with the failure of the nuclear AhR complex to bind genomic DRES. Two BapR T47D cell lines (C5 and CIO) were also isolated and both BAPR T47D cell variants exhibited decreased Aliresponsiveness. AhR MRNA levels were decreased in both variant cell lines indicating that decreased Ah-responsiveness may be related to decreased AhR gene expression. Although TCDD did not induce CYPIAI or decrease nuclear ER levels in the BapR MCF-7, TCDD inhibited estrogen-induced cell proliferation. |
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| Item Description: | Vita. "Major Subject: Toxicology". In title, numerals are used. |
| Physical Description: | xii, 201 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |