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The exposure of breast cancer cells to fulvestrant and tamoxifen modulates cell migration differently.

Lymperatou D, Giannopoulou E, Koutras AK, Kalofonos HP - Biomed Res Int (2013)

Bottom Line: We found that 17 β -estradiol (E2) demonstrated a protective role regarding cell migration and invasion.Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression.Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events.

View Article: PubMed Central - PubMed

Affiliation: Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, 26504 Rio, Greece.

ABSTRACT
There is no doubt that there are increased benefits of hormonal therapy to breast cancer patients; however, current evidence suggests that estrogen receptor (ER) blockage using antiestrogens is associated with a small induction of invasiveness in vitro. The mechanism by which epithelial tumor cells escape from the primary tumor and colonize to a distant site is not entirely understood. This study investigates the effect of two selective antagonists of the ER, Fulvestrant (Fulv) and Tamoxifen (Tam), on the invasive ability of breast cancer cells. We found that 17 β -estradiol (E2) demonstrated a protective role regarding cell migration and invasion. Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression. Furthermore, both tested agents increased expression of matrix metalloproteinases (MMPs) and enhanced invasive potential of breast cancer cells. These changes were in line with focal adhesion kinase (FAK) rearrangement. Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events. Although Fulv caused a less aggressive result compared to Tam, the benefits of hormonal therapy concerning invasion and metastasis yet remain to be investigated.

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Related in: MedlinePlus

The impact of E2 and the tested agents on Tyr397 FAK phosphorylation and F-actin rearrangement. MCF-7 cells exposed to E2 in a time course manner up to 60 min for detection of the maximum FAK phosphorylation. ERα and Tyr397 FAK localisation is indicated with green and red fluorescence, respectively. At the time point of 10 min, F-actin and Tyr397 FAK colocalisation (green and red fluorescence, resp.) was observed after the exposure of MCF-7 cells to the tested agents. C: control (untreated cells); E2: cells treated with 17β-estradiol; Fulv: cells treated with E2 + 100 nM Fulv; Tam: cells treated with E2 + 100 nM Tam; End: cells treated with E2 + 100 nM End; and 4-OH-T: cells treated with E2 + 100 nM 4-OH-T. The image is representative of three independent experiments using a magnification of 60X.
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fig8: The impact of E2 and the tested agents on Tyr397 FAK phosphorylation and F-actin rearrangement. MCF-7 cells exposed to E2 in a time course manner up to 60 min for detection of the maximum FAK phosphorylation. ERα and Tyr397 FAK localisation is indicated with green and red fluorescence, respectively. At the time point of 10 min, F-actin and Tyr397 FAK colocalisation (green and red fluorescence, resp.) was observed after the exposure of MCF-7 cells to the tested agents. C: control (untreated cells); E2: cells treated with 17β-estradiol; Fulv: cells treated with E2 + 100 nM Fulv; Tam: cells treated with E2 + 100 nM Tam; End: cells treated with E2 + 100 nM End; and 4-OH-T: cells treated with E2 + 100 nM 4-OH-T. The image is representative of three independent experiments using a magnification of 60X.

Mentions: FAK exerts a central role on cell migration and invasion, and its activation is correlated with malignant transformation [37, 38]. In addition, a specific phosphorylation at Tyr397 residue is correlated with Tam-resistance [22]. In MCF-7 cells, E2 exposure resulted in autophosphorylation of FAK in Tyr397 residue, which entails activation of FAK. This phenomenon was time dependent, and the highest phosphorylation was observed in 10 min (Figure 8). Thereafter, the phosphorylated signal was downregulated.


The exposure of breast cancer cells to fulvestrant and tamoxifen modulates cell migration differently.

Lymperatou D, Giannopoulou E, Koutras AK, Kalofonos HP - Biomed Res Int (2013)

The impact of E2 and the tested agents on Tyr397 FAK phosphorylation and F-actin rearrangement. MCF-7 cells exposed to E2 in a time course manner up to 60 min for detection of the maximum FAK phosphorylation. ERα and Tyr397 FAK localisation is indicated with green and red fluorescence, respectively. At the time point of 10 min, F-actin and Tyr397 FAK colocalisation (green and red fluorescence, resp.) was observed after the exposure of MCF-7 cells to the tested agents. C: control (untreated cells); E2: cells treated with 17β-estradiol; Fulv: cells treated with E2 + 100 nM Fulv; Tam: cells treated with E2 + 100 nM Tam; End: cells treated with E2 + 100 nM End; and 4-OH-T: cells treated with E2 + 100 nM 4-OH-T. The image is representative of three independent experiments using a magnification of 60X.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713599&req=5

fig8: The impact of E2 and the tested agents on Tyr397 FAK phosphorylation and F-actin rearrangement. MCF-7 cells exposed to E2 in a time course manner up to 60 min for detection of the maximum FAK phosphorylation. ERα and Tyr397 FAK localisation is indicated with green and red fluorescence, respectively. At the time point of 10 min, F-actin and Tyr397 FAK colocalisation (green and red fluorescence, resp.) was observed after the exposure of MCF-7 cells to the tested agents. C: control (untreated cells); E2: cells treated with 17β-estradiol; Fulv: cells treated with E2 + 100 nM Fulv; Tam: cells treated with E2 + 100 nM Tam; End: cells treated with E2 + 100 nM End; and 4-OH-T: cells treated with E2 + 100 nM 4-OH-T. The image is representative of three independent experiments using a magnification of 60X.
Mentions: FAK exerts a central role on cell migration and invasion, and its activation is correlated with malignant transformation [37, 38]. In addition, a specific phosphorylation at Tyr397 residue is correlated with Tam-resistance [22]. In MCF-7 cells, E2 exposure resulted in autophosphorylation of FAK in Tyr397 residue, which entails activation of FAK. This phenomenon was time dependent, and the highest phosphorylation was observed in 10 min (Figure 8). Thereafter, the phosphorylated signal was downregulated.

Bottom Line: We found that 17 β -estradiol (E2) demonstrated a protective role regarding cell migration and invasion.Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression.Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events.

View Article: PubMed Central - PubMed

Affiliation: Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, 26504 Rio, Greece.

ABSTRACT
There is no doubt that there are increased benefits of hormonal therapy to breast cancer patients; however, current evidence suggests that estrogen receptor (ER) blockage using antiestrogens is associated with a small induction of invasiveness in vitro. The mechanism by which epithelial tumor cells escape from the primary tumor and colonize to a distant site is not entirely understood. This study investigates the effect of two selective antagonists of the ER, Fulvestrant (Fulv) and Tamoxifen (Tam), on the invasive ability of breast cancer cells. We found that 17 β -estradiol (E2) demonstrated a protective role regarding cell migration and invasion. Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression. Furthermore, both tested agents increased expression of matrix metalloproteinases (MMPs) and enhanced invasive potential of breast cancer cells. These changes were in line with focal adhesion kinase (FAK) rearrangement. Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events. Although Fulv caused a less aggressive result compared to Tam, the benefits of hormonal therapy concerning invasion and metastasis yet remain to be investigated.

Show MeSH
Related in: MedlinePlus