Expression of estrogenicity genes in a lineage cell culture model of human breast cancer progression

Fu, Jiaqi; Weise, Amy; Falany, Josie L.; Falany, Charles N.; Thibodeau, Bryan J.; Miller, Fred R.; Kocarek, Thomas A.; Runge‐Morris, Melissa

doi:10.1007/s10549-009-0363-8

Cited by 31 publications

(34 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently reported that SULT1E1 mRNA content is markedly increased when replicating MCF10A cells become confluent (Fu et al, 2010), indicating that SULT1E1 expression is regulated according to the confluence of these cells. In comparison, in an earlier study in which we profiled the expression of cytochrome P450 transcripts in MCF10A cells, two cytochromes P450, CYP1A1 and CYP1S1, were expressed in preconfluent MCF10A cells but not in confluent MCF10A cells (Thomas et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

“…In this manner, SULT1E1 expression in breast epithelial cells probably limits the mitogenic effects of estrogen, thereby reducing the risk for breast cancer development (Falany et al, 1995). SULT1E1 is expressed in human breast epithelial cells as well as in the MCF10A cell line, a model of normal human breast epithelial cells, but is down-regulated in many breast cancer cell lines, suggesting that this brake against estrogen mitogenicity is often lost during neoplastic transformation (Falany and Falany, 1996;Fu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. We recently reported that SULT1E1 expression is low in preconfluent MCF10A human breast epithelial cells but increases when the cells become confluent. Pulse-chase labeling experiments with 5-bromouridine demonstrated that the confluence-mediated increase in SULT1E1 expression was due to increased mRNA synthesis. Because aryl hydrocarbon receptor (AhR) activation has been shown to suppress SULT1E1 expression and loss of cell-cell contact has been shown to activate the AhR in other cell types, we tested whether the confluence-associated changes in SULT1E1 expression were mediated by the AhR. Relative to confluent MCF10A cells, preconfluent cells had higher levels of CYP1A1 mRNA and greater activation of an AhR-responsive luciferase reporter, demonstrating that the AhR was active in the preconfluent cells. AhR and aryl hydrocarbon receptor nuclear translocator mRNA and protein levels were also higher in preconfluent than in confluent cultures. Treatment of preconfluent cells with the AhR antagonist, 3Ј-methoxy-4Ј-nitroflavone (MNF), or AhR knockdown significantly increased SULT1E1 expression. MCF10A cells stably transfected with a luciferase reporter containing ϳ7 kilobases of the SULT1E1 5Ј-flanking region showed both MNF-and confluence-inducible luciferase expression. Preconfluent cells transiently transfected with the reporter showed both MNF treatment-and AhR knockdown-mediated luciferase induction, but mutation of a computationally predicted dioxin response element (DRE) at nucleotide (nt) Ϫ3476 did not attenuate these effects. These results demonstrate that SULT1E1 expression in MCF10A cells is transcriptionally regulated by confluence through a suppressive action of the AhR, which is not mediated through a DRE at nt Ϫ3476.

show abstract

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, we tested whether the induction of EST plays a role in the anti-breast cancer effect of TM208. EST shows the highest affinity for E2 and estrone [15] , whereas other SULTs, such as SULT1A1 and SULT2A1, exhibit some affinities for E2 and estrone, which are only found at non-physiological high concentrations [14,41] . Not counting EST, SULT1A1 was reported to play the most crucial role in the sulfation of intratumoral estrogens by its contribution to the conjugation of the metabolites of E2 (such as 4-OH-E2 and 2-methoxy-E2) metabolized by CYP1B1 and 1A1 [14,42] .…”

Section: Discussionmentioning

confidence: 99%

“…EST shows the highest affinity for E2 and estrone [15] , whereas other SULTs, such as SULT1A1 and SULT2A1, exhibit some affinities for E2 and estrone, which are only found at non-physiological high concentrations [14,41] . Not counting EST, SULT1A1 was reported to play the most crucial role in the sulfation of intratumoral estrogens by its contribution to the conjugation of the metabolites of E2 (such as 4-OH-E2 and 2-methoxy-E2) metabolized by CYP1B1 and 1A1 [14,42] . However, as for the parent levels of E2 in the tumor, all available results of previous studies have demonstrated that the intratumoral E2 concentrations were at physiological (nanomolar) levels even when expressed as pg/g tissue or pmol/g tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The sulfation of estrogens by sulfotransferase (SULT) is the most important pathway for inactivating estrogens, including estrone (E1) and 17β-estradiol (E2). The main SULT isoforms that catalyze the sulfation of estrogen in the human body include SULT1E1, SULT1A1, SULT2A1, and SULT2B1, as well as others [8,9,11,14] . Among these isoforms, estrogen sulfotransferase (EST, SULT1E1) plays the most important role in estrogen inactivation under physiological conditions due to its high affinity for estrogens [15] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Chen

Song

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Sulfotransferase-catalyzed sulfation is the most important pathway for inactivating estrogens. Thus, activation of estrogen sulfotransferase (EST) may be an alternative approach for the treatment of estrogen-dependent breast cancer. In this study we investigated the involvement of EST in anti-breast cancer effects of the dithiocarbamate derivative TM208 in vitro and in vivo. Methods: The viability of human breast cancer MCF-7 cells was determined using a SBB assay. Nude mice bearing MCF-7 cells were orally administered TM208 (50 and 150 mg·kg -1 ·d -1 ) for 18 days. The xenograft tumors and uteri were collected. The mRNA expression of EST was examined with real-time PCR. EST protein was detected with Western blot, ELISA or immunohistochemical staining assays. A radioactive assay was used to measure the EST activity. Uterotropic bioassay was used to examine the uterine estrogen responses. Results: Treatment with TM208 (10, 15 and 20 µmol/L) concentration-dependently increased EST expression in MCF-7 cells in vitro. Co-treatment with triclosan, an inhibitor of sulfonation, abolished TM208-induced cytotoxicity in MCF-7 cells. TM208 exhibited an apparent anti-estrogenic property: it exerted more potent cytotoxicity in E2-treated MCF-7 cells. In the nude mice bearing MCF-7 cells, TM208 administration time-dependently increased the expression and activity of EST, and blocked the gradual increase of E2 concentration in the xenograft tumors. Furthermore, TM208 administration blocked the estrogens-stimulated uterine enlargement. Tamoxifen, a positive control drug, produced similar effects on the expression and activity of EST in vitro and in vivo. Conclusion: The induction of EST and reduction of estrogen concentration contribute to the anti-breast cancer action of TM208 and tamoxifen. TM208 may be developed as anticancer drug for the treatment of estrogen receptor-positive breast cancer.

show abstract

Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,3′-diindolylmethene in human breast epithelial cell lines

et al. 2012

View full text Add to dashboard Cite

PurposeThe aim of this study was to evaluate the effect of white cabbage and sauerkraut juices of different origin and indole-3-carbinol (I3C) and diindolylmethane (DIM) on expression of CYP19 gene encoding aromatase, the key enzyme of estrogen synthesis.MethodsHuman breast cell lines (MCF7, MDA-MB-231 and MCF10A) were examined to compare the action of cabbage juices versus their active components (I3C, DIM). Real-time PCR and Western blot were used in order to analyse CYP19 mRNA and protein, respectively.ResultsRemarkable differences in the effect on CYP19 transcript and protein level were found between the cabbage juices (in 2.5–25 mL/L concentrations) and indoles (in 2.5–50 μM doses) in the three cell lines. While cabbage juices at the lower doses diminished the aromatase expression in nontumorigenic/immortalized MCF10A breast cells (0.25–0.86-fold change, P < 0.05), I3C and DIM were more efficient in decreasing the aromatase expression in estrogen-dependant MCF7 breast cancer cells (0.24–0.82-fold change, P < 0.05). Inhibition of aromatase by juice obtained from cabbage grown on industrial farm was correlated with the induction of apoptosis (1.7–1.8-fold change, P < 0.01) in MCF10A cells. In estrogen-independent MDA-MB-231 cells, up-regulation of CYP19 expression by I3C and DIM (1.5–2.0-fold change, P < 0.05) was observed. Similarly, in MCF7 cells juices increased aromatase expression (1.1–2.2-fold change, P < 0.05).ConclusionThese results, particularly that obtained in nontumorigenic/immortalized MCF10A cells, suggest that chemopreventive activity of cabbage against breast cancer observed in epidemiological studies may be partly explained by inhibition of the aromatase expression.

show abstract

Expression of estrogenicity genes in a lineage cell culture model of human breast cancer progression

Cited by 31 publications

References 51 publications

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,3′-diindolylmethene in human breast epithelial cell lines

Contact Info

Product

Resources

About