Differences in protein kinase C and estrogen receptor alpha, beta expression and signaling correlate with apoptotic sensitivity of MCF-7 breast cancer cell variants.

Burow, Matthew E.; Weldon, Christopher B.; Chiang, Tung-Chin; Tang, Yan; Collins‐Burow, Bridgette M.; Rolfe, Kevin W.; Li, Shuanfang; McLachlan, John A.; Beckman, Barbara S.

doi:10.3892/ijo.16.6.1179

Cited by 16 publications

(13 citation statements)

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“…The precise roles of ERa and ERb on the proliferation and protection are still unknown. They have been so far shown to exhibit unique properties on the cell cycle progression, activation of the mitogen-activated protein kinase pathway and protein kinase C expression (Burow et al, 2000;Wade et al, 2001;Liu et al, 2002;Paruthiyil et al, 2004;Strom et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity

et al. 2005

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We have investigated the effect of estrogen on p53 cellular location and its influence on tumor cell susceptibility to tumor necrosis factor (TNF)-mediated cytotoxic action. For this purpose, we have used the TNF-sensitive human breast adenocarcinoma MCF-7 and its derivative, the TNF-resistant 1001 clone. Our data indicate that although estrogen receptor (ER)a is present in both cell lines, estrogen treatment (1 Â 10 À8 M) has an influence only on the MCF-7 cells and protects these cells from the TNF cytotoxicity. This protective effect is associated with translocation of p53 from the nucleus to the cytoplasm in p53 wild-type MCF-7 and not in p53-mutated 1001 cells. The translocation of p53 in MCF-7 cells results in a decrease in its transcriptional activity, as revealed by diminished p21 WAF1/CIP1 induction and an altered ratio of Bax and Bcl-2 proteins. The estrogen-induced effects are reversed by the selective estrogen inhibitor 182, 780 (1 Â 10 À6 M). Interestingly, transient transfection of MCF-7 cells with ERb but not ERa cDNA encoding plasmid results in retention of p53 in the nucleus, a subsequent potentiation of its transcriptional activity, and in an increased MCF-7 sensitivity to TNF. The estrogen effects on p53 location and transcriptional activity may involve the mdm2 protein since both events were reversed following MCF-7 transfection with plasmid encoding the ARF cDNA. These studies suggest that estrogen-induced MCF-7 cell survival in the presence of TNF requires a transcriptionally active p53 and, more importantly, indicate that introduction of ERb can attenuate the estrogen effects on the p53 protein location, its transcriptional activity and also results in a potentiation of cell sensitivity to TNF-mediated cell death.

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Section: Introductionmentioning

confidence: 99%

Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity

et al. 2005

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“…Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was performed as previously described (62). Briefly, RNA was extracted using an Ultraspec RNA isolation kit (Biotecx Lab, Houston, TX).…”

Section: Chemicalsmentioning

confidence: 99%

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Frigo

Burow

Mitchell

et al. 2002

Environ Health Perspect

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Endocrine-disrupting organochlorines, such as the pesticide dichlorodiphenyltrichloroethane (DDT), bind to and activate estrogen receptors (ERs), thereby eliciting estrogen-like effects. Although ERs function predominantly through activation of transcription via estrogen-responsive elements, both ERs, alpha and ss, can interact with various transcription factors such as activator protein-1 (AP-1). Additionally, estrogens may regulate early signaling events, suggesting that the biological effects of environmental estrogens may not be mediated through classic ER (alpha and ss) activity alone. We hypothesized that known environmental estrogens, such as DDT and its metabolites, activate AP-1-mediated gene transactivation through both ER-dependent and ER-independent means. Using two Ishikawa human endometrial adenocarcinoma cell line variants that we confirmed to be estrogen responsive [Ishikawa(+)] and estrogen unresponsive [Ishikawa(-)], we generated stably transfected AP-1 luciferase cell lines to identify the role of an estrogen-responsive mechanism in AP-1-mediated gene expression by various stimuli. Our results demonstrate that DDT and dichlorodiphenyldichloroethane (DDD) were the most potent activators of AP-1 activity; 2,2-bis(p-chlorophenyl) acetic acid failed to activate. Although stimulated in both Ishikawa(+) and Ishikawa(-) cells by DDT and its congeners, AP-1 activation was more pronounced in the estrogen-unresponsive Ishikawa(-) cells. In addition, DDT, DDD, and dichlorodiphenyldichloroethylene (DDE) could also stimulate AP-1 activity in the estrogen-unresponsive human embryonic kidney 293 cells using a different promoter context. Thus, our data demonstrate that DDT and its metabolites activate the AP-1 transcription factor independent of ER (alpha or ss) status.

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“…The ERα-positive MCF-7 breast carcinoma cells (N variant) (39), ERα-positive Ishikawa endometrial carcinoma cells (Ishikawa(+))(38), ERα-negative Human Embryonic Kidney 293 (HEK293) and ERα-negative HepG2 cells were cultured in 150 cm 2 culture flasks in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal bovine serum (FBS) (Gibco-BRL, Gaithersburg, MD), as well as BME and MEM amino acids, L-glutamine, sodium pyruvate, and penicillin-streptomycin (diluted in the medium to a 1× concentration from either 100× or 50× stocks for a final concentration of 1%), and porcine insulin (10 −8 M) (Sigma Chemical Co., St. Louis, MO). The culture flasks were maintained in a cell incubator at a humidified atmosphere of 5% CO 2 and 95% air at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

Collins‐Burow

Antoon

Frigo

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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Flavonoid phytochemicals act as both agonists and antagonists of the human estrogen receptors (ERs). While a number of these compounds act by directly binding to the ER, certain phytochemicals, such as the flavonoid compounds chalcone and flavone, elicit antagonistic effects on estrogen signaling independent of direct receptor binding. Here we demonstrate both chalcone and flavone function as cell type-specific selective ER modulators. In MCF-7 breast carcinoma cells chalcone and flavone suppress ERα activity through stimulation of the stress-activated members of the mitogen-activated protein kinase (MAPK) family: c-Jun N-terminal kinase (JNK)1 and JNK2. The use of dominant-negative mutants of JNK1 or JNK2 in stable transfected cells established that the antiestrogenic effects of chalcone and flavone required intact JNK signaling. We further show that constitutive activation of the JNK pathway partially suppresses estrogen (E2)-mediated gene expression in breast, but not endometrial carcinoma cells. Our results demonstrate a role for stress-activated MAPKs in the cell type-specific regulation of ERα function.

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Differences in protein kinase C and estrogen receptor alpha, beta expression and signaling correlate with apoptotic sensitivity of MCF-7 breast cancer cell variants.

Cited by 16 publications

References 0 publications

Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity

Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

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