An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol

Jiang, Shun Yuan; Wolf, Douglas M.; Yingling, Jonathan M.; Chang, Chawnshang; Jordan, V. Craig

doi:10.1016/0303-7207(92)90104-e

Cited by 112 publications

(111 citation statements)

References 34 publications

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“…Before gene expression microarray studies were carried out, the estrogen-dependent WS8 (29-31), ED-resistant but apoptosis-refractory 2A (25,30,31), and apoptosis-sensitive 5C cells (24,29,32) were characterized to confirm previously reported growth responses, biomarker status, and estrogen response element (ERE) -regulated transcriptional activity (SI Results and Discussion, SI Methods, and Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

“…By describing and defining these molecular events, refractory cells may be manipulated to respond to estrogen-induced apoptosis. To begin to address the question, we have developed a series of MCF-7 variants that are either estrogen-dependent for growth (MCF-7:WS8 cells) (29)(30)(31) or resistant to estrogen deprivation (ED) and refractory (MCF-7:2A) (25,30,31) or sensitive (MCF-7:5C) (24,29,32) to E 2 -induced apoptosis. We previously reported changes in gene expression among these cell lines by Affymetrix-based microarray analysis under estrogen-free conditions (33).…”

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confidence: 99%

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Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

Ariazi

Cunliffe

Lewis-Wambi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

147

190

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This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2009.Contributed by V. Craig Jordan, September 14, 2011 (sent for review June 21, 2011) In laboratory studies, acquired resistance to long-term antihormonal therapy in breast cancer evolves through two phases over 5 y. Phase I develops within 1 y, and tumor growth occurs with either 17β-estradiol (E 2 ) or tamoxifen. Phase II resistance develops after 5 y of therapy, and tamoxifen still stimulates growth; however, E 2 paradoxically induces apoptosis. This finding is the basis for the clinical use of estrogen to treat advanced antihormone-resistant breast cancer. We interrogated E 2 -induced apoptosis by analysis of gene expression across time (2-96 h) in MCF-7 cell variants that were estrogen-dependent (WS8) or resistant to estrogen deprivation and refractory (2A) or sensitive (5C) to E 2 -induced apoptosis. We developed a method termed differential area under the curve analysis that identified genes uniquely regulated by E 2 in 5C cells compared with both WS8 and 2A cells and hence, were associated with E 2 -induced apoptosis. Estrogen signaling, endoplasmic reticulum stress (ERS), and inflammatory response genes were overrepresented among the 5C-specific genes. The identified ERS genes indicated that E 2 inhibited protein folding, translation, and fatty acid synthesis. Meanwhile, the ERS-associated apoptotic genes Bcl-2 interacting mediator of cell death (BIM; BCL2L11) and caspase-4 (CASP4), among others, were induced. Evaluation of a caspase peptide inhibitor panel showed that the CASP4 inhibitor z-LEVD-fmk was the most active at blocking E 2 -induced apoptosis. Furthermore, z-LEVD-fmk completely prevented poly (ADP-ribose) polymerase (PARP) cleavage, E 2 -inhibited growth, and apoptotic morphology. The up-regulated proinflammatory genes included IL, IFN, and arachidonic acid-related genes. Functional testing showed that arachidonic acid and E 2 interacted to superadditively induce apoptosis. Therefore, these data indicate that E 2 induced apoptosis through ERS and inflammatory responses in advanced antihormone-resistant breast cancer.aromatase inhibitor | antihormonal resistance | estrogen receptor | gene expression microarrays | selective estrogen receptor modulator E lucidation of the basic structure function relationships of synthetic estrogens based on either stilbene (1) or triphenylethylene (2) was a landmark achievement that continues to have major therapeutic implications to this day. The first successful chemical therapy for the treatment of any cancer was the use of high-dose synthetic estrogen for the treatment of metastatic breast cancer (3). Response rates for patients who were more than a decade beyond menopause were about 30%. Importantly, treatment near menopause was ineffective, and therefore, tumor responsiveness was related to the duration of estrogen deprivation. In 1970, Alexander Haddow commented that "the extraordinary extent of tumor regression observed in...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

Ariazi

Cunliffe

Lewis-Wambi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

147

190

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“…MCF-7/WS8 mammary carcinoma cells were used in all studies in which MCF-7 cells are indicated; they were clonally derived from MCF-7 cells by selection for sensitivity to growth stimulation by E 2 (46,47). BT-474 cells were obtained from the American Type Culture Collection (Manassas, VA).…”

Section: Cell Linesmentioning

confidence: 99%

Estrogen-Related Receptor α1 Transcriptional Activities Are Regulated in Part via the ErbB2/HER2 Signaling Pathway

Ariazi

Kraus

Farrell

et al. 2007

Molecular Cancer Research

105

106

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We previously showed that (a) estrogen-related receptor A1 (ERRA1) down-modulates estrogen receptor (ER) -stimulated transcription in low ErbB2 -expressing MCF-7 mammary carcinoma cells, and (b) ERRA and ErbB2 mRNA levels positively correlate in clinical breast tumors. We show here that ERRA1 represses ERA-mediated activation in MCF-7 cells because it failed to recruit the coactivator glucocorticoid receptor interacting protein 1 (GRIP1) when bound to an estrogen response element. In contrast, ERRA1 activated estrogen response element -and ERR response element -mediated transcription in ERA-positive, high ErbB2 -expressing BT-474 mammary carcinoma cells, activation that was enhanced by overexpression of GRIP1. Likewise, regulation of the endogenous genes pS2, progesterone receptor, and ErbB2 by ERRA1 reflected the cell type -specific differences observed with our reporter plasmids. Importantly, overexpression of activated ErbB2 in MCF-7 cells led to transcriptional activation, rather than repression, by ERRA1. Two-dimensional PAGE of radiophosphate-labeled ERRA1 indicated that it was hyperphosphorylated in BT-474 relative to MCF-7 cells; incubation of these cells with anti-ErbB2 antibody led to reduction in the extent of ERRA1 phosphorylation. Additionally, mitogen-activated protein kinases (MAPK) and Akts, components of the ErbB2 pathway, phosphorylated ERRA1 in vitro. ERRA1-activated transcription in BT-474 cells was inhibited by disruption of ErbB2/epidermal growth factor receptor signaling with trastuzumab or gefitinib or inactivation of downstream components of this signaling, MAPK kinase/MAPK, and phosphatidylinositol-3-OH kinase/ Akt, with U0126 or LY294002, respectively. Thus, ERRA1 activities are regulated, in part, via ErbB2 signaling, with ERRA1 likely positively feedback-regulating ErbB2 expression. Taken together, we conclude that ERRA1 phosphorylation status shows potential as a biomarker of clinical course and antihormonal-and ErbB2-based treatment options, with ERRA1 serving as a novel target for drug development. (Mol Cancer Res 2007;5(1):71 -85)

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“…2 The cell line ZR75-30 was obtained from the American Type Culture Collection (Manassas, Va). The cell lines T47D/C42, MCF7/5C, and MD-MBA231/S30 were kindly provided by Dr Craig Jordan (Northwestern University) and are either estrogen-unresponsive (MCF7/5C), 8 lack the ER (T47D/C42), 9 or are stably transfected with the full-length human ER (MD-MBA231/ S30). 10 These three cell lines were grown in their respective modified media: T47D/C42 and MCF7/5C, RPMI 1640 without phenol red, 10% charcoal-stripped fetal calf serum, and 0.2 international units of bovine insulin/mL; MD-MBA231/S30, minimum essential medium without phenol red, 10% charcoalstripped fetal calf serum, 0.2 international units of bovine insulin/mL, and 500 g/mL G418.…”

Section: Cell Linesmentioning

confidence: 99%

Breast cancer-specific expression of the Candida albicans cytosine deaminase gene using a transcriptional targeting approach

et al. 2000

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We constructed a series of adenoviral (Ad) vectors that express the Candida albicans cytosine deaminase (CD) suicide gene under the transcriptional control of either the human ␣-lactalbumin (ALA) or ovine ␤-lactoglobulin (BLG) promoter (Ad.ALA.CD and Ad.BLG.CD, respectively). The Ad.ALA.CD and the Ad.BLG.CD vectors converted the prodrug 5-fluorocytosine (5-FC) to the toxic nucleotide analog 5-fluorouracil in a breast cancer cell-specific manner, with a conversion rate of 40% and 52% in T47D cells and 50% and 41% in MCF7 cells, respectively. No significant conversion (Յ3%) was observed in an immortalized nontumorigenic breast epithelial cell line (MCF10A) and a human osteosarcoma cell line (U2OS). Adenovirus vector-based prodrug conversion of the 5-FC in T47D and MCF7 in the presence of 1 mg/mL of 5-FC led to cytotoxicity that resulted in a nearly complete cell death (Ն90%) after 5 days, whereas MCF10A and U2OS cells remained resistant (Յ10%). Nude mice harboring T47D-derived breast tumors that were injected intratumorally (i.t.) with therapeutic adenovirus vectors at a dose of 2 ϫ 10 8 plaque-forming units and treated systemically with 5-FC at a concentration of 500 mg/kg/day showed a marked reduction in tumor mass within 30 days when compared with animals that received vector alone. Animal survival was significantly prolonged after 72 days in mice treated with therapeutic vectors in conjunction with prodrug when compared with control animals. These preclinical data are sufficiently promising to warrant further studies of this transcriptional targeting approach to breast cancer treatment.

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An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol

Cited by 112 publications

References 34 publications

Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

Estrogen-Related Receptor α1 Transcriptional Activities Are Regulated in Part via the ErbB2/HER2 Signaling Pathway

Breast cancer-specific expression of the Candida albicans cytosine deaminase gene using a transcriptional targeting approach

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