Ligand-Modulated Regulation of Progesterone Receptor Messenger Ribonucleic Acid and Protein in Human Breast Cancer Cell Lines

Read, Linnea D.; Snider, Catherine E.; Miller, Jean S.; Greene, Geoffrey L.; Katzenellenbogen, Benita S.

doi:10.1210/mend-2-3-263

Cited by 228 publications

(135 citation statements)

References 20 publications

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“…Similar results were observed when MCF-7 cells were incubated with either low or high E2 concentrations. Two concentrations of E2 were used because it has been reported that E2 can modulate HER2 expression in MCF-7 cells after short incubation periods, depending on E2 concentration [18][19][20][21][22].…”

Section: E2 Regulates Her2 Expression By a Mechanism Independent Of Dmentioning

confidence: 99%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

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Tumor cells utilize inappropriate epithelialmesenchymal transition (EMT) mechanisms during the invasive process. It is becoming increasingly clear that estradiol (E2) induces breast cancer cell progression and enhances EMT; however, the mechanisms associated with this are unclear. We investigated the role of E2 on the expression and intracellular localization of the tight junction (TJ)-associated proteins, zonula occluden 1 (ZO-1), ZO-1-associated nucleic acid binding (ZONAB), and occludin, on the activation of cSrc and human epidermal growth factor receptor 2 (HER2) expression and cellular migration in the estrogen receptor (ER)-positive breast cancer cell lines, MCF-7 and T47D. WeNovelty and Impact Statements We demonstrated that estrogen is able to induce tight junction (TJ) disruption in two breast cancer cell lines through the activation of c-Src. Ablated expression of the novel epithelial marker CRB3 could lead to increased cell migration. Based on our findings, we propose a novel estrogen-induced TJ pathway associated with breast cancer cell motility and, eventually, to metastasis. demonstrated that 1 nM E2 elicits c-Src activation after 15 min. The p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and increased expression of HER2 mRNAs. These changes correlate with decreased expression of the epithelial markers occludin and CRB3 and increased synthesis of N-cadherin. This led to increased MCF-7 cell migration induced by E2, even in the presence of a cell proliferation inhibitor. Incubation with ICI 182,780 (Fulvestrant), an ER antagonist, precluded the effects of E2 on c-Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, and migration of MCF-7 cells. Our findings suggest that E2 promotes TJ disruption during tumor progression and increases cell motility. We propose a novel pathway where estrogens promote EMTassociated mechanisms that possibly lead to metastasis.

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Section: E2 Regulates Her2 Expression By a Mechanism Independent Of Dmentioning

confidence: 99%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

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“…c-erbB-2 can be inhibited by steroids and cytokines (Read et al 1990: De Bortoli et al 1992Marth et al 1992;Kalthoff et al 1993;Nehme et al 1995). We and others have demonstrated a negative interaction between the oestrogen receptor and c-erbB-2 (Read et al 1990;Grunt et al 1995;Saceda et al, 1996). Recently, we have also shown that c-erbB receptor activation elevates the expression of RAR-a in SK-BR-3 cells (Flicker et al, 1997).…”

mentioning

confidence: 90%

“…which belongs to the membrane-anchored type 1 (epidermal growth factor receptorrelated) receptor tyrosine kinases and which becomes indirectly activated by epidermal growth factor-like ligands (for review see Grunt and Huber, 1994). c-erbB-2 can be inhibited by steroids and cytokines (Read et al 1990: De Bortoli et al 1992Marth et al 1992;Kalthoff et al 1993;Nehme et al 1995). We and others have demonstrated a negative interaction between the oestrogen receptor and c-erbB-2 (Read et al 1990;Grunt et al 1995;Saceda et al, 1996).…”

mentioning

confidence: 98%

Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells

Grunt

Dittrich²,

Offterdinger³

et al. 1998

Br J Cancer

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Summary We investigated the effects of all-trans retinoic acid (ATRA) and fenretinide (4-HPR) on c-erbB-2 expression in SK-BR-3, and MCF-7 breast cancer cells and on the growth, differentiation, apoptosis and cisplatin (CDDP) sensitivity of SK-BR-3 cells. It has been reported that oestrogen inhibits c-erbB-2 in oestrogen receptor-positive breast cancer cells. Using ELISA, Westem and Northem analysis we have demonstrated that ATRA and 4-HPR exert similar effects down-regulating c-erbB-2 protein and mRNA in c-erbB-2-overexpressing SK-BR-3 and BT-474 and in normally expressing MCF-7 cells. Both retinoids inhibit SK-BR-3 cell growth. ATRA induces cellular enlargement and flattening, suggesting epithelial differentiation. 4-HPR causes nuclear and cytoplasmic condensation, DNA fragmentation and externalization of phosphabdylserine, indicating apoptosis. c-erbB-2 expression/activity has been linked to sensitivity against CDDP. Therefore, combinations of ATRA or 4-HPR with CDDP were tested for their anti-proliferative activity. Retinoid-conditioned cells were either exposed to retinoid and CDDP (schedule 1, 'continuous retinoid treatment') or to CDDP alone (schedule II, 'retinoid pretreatment'). This retinoid-conditioning followed by CDDP ± retinoid yields stronger growth inhibition compared with unconditioned cells, which were exposed to CDDP ± retinoid (schedule 111, 'no retnoid pretreatment'). The inefficacy of schedule Ill indicates that retioidconditioning is essential for the improvement of the antiproliferative effect. The interactions in schedules I and II are synergistic for ATRA and CDDP, but slightly antagonistic for 4-HPR and CDDP. However, 4-HPR + CDDP is more effective in growth inhibition than each drug alone.

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“…It is also known that anti-oestrogens are less effective for the treatment of patients with breast cancer overexpressing HER1 or HER2 together with ER (Ross and Fletcher, 1998). Previous experiments have indicated that oestrogen down-regulates HER2 in ER-positive breast cancer cells and anti-oestrogen reverses the oestrogeninduced decrease in HER2 expression (Read et al, 1990). Thus, it is conceivable that anti-oestrogen may activate a HER2-signalling pathway and may cause resistance to anti-oestrogen.…”

mentioning

confidence: 99%

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

et al. 2000

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Summary Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, but most of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2 signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combined therapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect of combined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, on the cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combined treatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, but showed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, which express no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1-S blockade and apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for the treatment of patients with breast cancer expressing both ER and HER2.

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Ligand-Modulated Regulation of Progesterone Receptor Messenger Ribonucleic Acid and Protein in Human Breast Cancer Cell Lines

Cited by 228 publications

References 20 publications

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

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