Mechanism of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells

Wang, X.; Porter, Weston W.; Krishnan, Venkatesh; Narasimhan, T.R.; Safe, Stephen

doi:10.1016/0303-7207(93)90106-t

Cited by 72 publications

(27 citation statements)

References 39 publications

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“…Studies in this laboratory have focused on determining the regulation of Ah responsiveness in human breast cancer cell lines using induction of CYPlAI and inhibition of oestrogeninduced gene expression as models (Harris et al, 1989;Arellano et al, 1993;Moore et al, 1993;Wang et al, 1993;Thomsen et al, 1994;Chaloupka et al, 1995). Several reports suggest that induction of CYPlAI in human breast cancer cells by AhR agonists requires a functional ER (Jaiswal et al, 1985;Ivy et al, 1988;Pasanen et al, 1988;Harris et al, 1989;Thomsen et al, 1991Thomsen et al, ,1994.…”

Section: Discussionmentioning

confidence: 99%

Effect of transient expression of the oestrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells

Thomsen²,

Porter³

et al. 1996

Br J Cancer

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Summary Hs578T human breast cancer cells are an oestrogen receptor (ER)-negative cell line. Treatment of these cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in formation of a 6.9 S nuclear aryl hydrocarbon (Ah) receptor complex, which bound to a [32P]dioxin-responsive element in a gel electrophoretic mobility shift assay. However, TCDD does not induce CYPlAl gene expression or chloramphenicol acetyl transferase (CAT) activity in cells transiently transfected with pRNHllc or pMCAT5.12, which are Ahresponsive plasmids derived from the 5'-flanking region of the human and murine CYP1A1 genes respectively. Restoration of Ah responsiveness was investigated by co-transfecting Hs578T cells with pRNH1 lc or pMCAT5.12 and plasmids that express the ER (hER), Ah receptor (AhR) and AhR nuclear translocator (Arnt) proteins. ER expression resulted in significantly increased basal CAT activity; however, TCDD did not induce CAT activity in the transiently transfected cells. Expression of the AhR or Arnt proteins did not alter basal or inducible CAT activity. Expression of N-or C-terminal truncated ER in Hs578T resulted in differential regulation of Ah responsiveness. In Hs578T cells transiently expressing the ER, which contains Cterminal deletions (amino acids 282-595), basal CAT activity was also increased; however, Ah responsiveness was not restored. In contrast, transient expression of N-terminal-deleted (amino acids 1 -178) ER resulted in a marked decrease in basal CAT activity but a restoration of Ah responsiveness. These results suggest that basal and inducible CAT activity in Hs578T cells transiently transfected with pRNHl lc is modulated differentially by ER domains that are present in the N-and C-terminal regions of the ER.

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Section: Discussionmentioning

confidence: 99%

Effect of transient expression of the oestrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells

Thomsen²,

Porter³

et al. 1996

Br J Cancer

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“…Sewall et al 1993). Effects ofTCDD on the estrogen (Wang et al 1993) and progesterone receptors (Harper et al 1994) also have been noted. Several cytokines have been implicated in modUlation of AHR gene regulation (Abdel-Razzak et al 1993).…”

Section: Ahr and Phosphorylationmentioning

confidence: 92%

Mechanisms of action for aryl hydrocarbon receptor ligands in the PLHC-1 cell line

Hestermann¹

1999

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“…In addition to being linked to the pathoses listed above, TCDD and other AhR ligands may have anti-estrogenic effects as demonstrated by their ability to inhibit a broad spectrum of estrogeninduced responses in rodents and breast cancer cell lines (Harris et al 1990, Safe et al 1991, Wang et al 1993, Gierthy et al 1994, Harper et al 1994, Nodland et al 1997. However, as discussed below, resveratrol might also possess estrogen-like activity, although this is less likely.…”

Section: Figurementioning

confidence: 99%

Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol

Singh¹,

Casper²,

Fritz³

et al. 2000

Journal of Endocrinology

131

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Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smokeassociated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4 -trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0·01 vs control) in the presence of 10 9 M TCDD and these effects were reversed by 10 6 M resveratrol (P<0·05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10 10 M) caused an approximately 33% reduction in AP activity, which was abrogated by 3·5 10 7 M resveratrol. TCDD also induced a marked reduction in mineralization (75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss.

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Mechanism of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells

Cited by 72 publications

References 39 publications

Effect of transient expression of the oestrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells

Effect of transient expression of the oestrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells

Mechanisms of action for aryl hydrocarbon receptor ligands in the PLHC-1 cell line

Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol

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