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Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta.

Flamini MI, Gauna GV, Sottile ML, Nadin BS, Sanchez AM, Vargas-Roig LM - J. Cell. Mol. Med. (2014)

Bottom Line: The retinoic acid receptor β (RARβ) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis.On the contrary, the addition of the selective retinoid RARβ-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition.When RARβ gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c-Src and FAK expressions.

View Article: PubMed Central - PubMed

Affiliation: Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentina, Mendoza, Argentina.

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Related in: MedlinePlus

(A) MCF7 cells were treated with retinoic acid (RA) in different concentrations (10−7/10−5 M) and cell migration was imaged after 72 hrs. (B) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. (C) T47D cells were treated with RA (10−6 M) and the synthetic agonist retinoids, selective for RARα Agonist (BMS753), RARβ Agonist (BMS453) and RARγ Agonist (BMS961), and the synthetic antagonist retinoids selective for RARα (BMS195614) plus RA (10−6 M). All retinoids were incubated at 10−6 M for 72 hrs. Cell migration was imaged after 72 hrs. (D) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. These experiments were performed in triplicates and representative images are shown.
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fig02: (A) MCF7 cells were treated with retinoic acid (RA) in different concentrations (10−7/10−5 M) and cell migration was imaged after 72 hrs. (B) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. (C) T47D cells were treated with RA (10−6 M) and the synthetic agonist retinoids, selective for RARα Agonist (BMS753), RARβ Agonist (BMS453) and RARγ Agonist (BMS961), and the synthetic antagonist retinoids selective for RARα (BMS195614) plus RA (10−6 M). All retinoids were incubated at 10−6 M for 72 hrs. Cell migration was imaged after 72 hrs. (D) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. These experiments were performed in triplicates and representative images are shown.

Mentions: The effect of RA on breast cancer cell migration was then tested in a dose–response experiment. To distinguish cell migration from cell proliferation, Cytosine-β-d-arabinofuranoside hydrochloride (10 μM), a selective inhibitor of DNA strand separation that does not block RNA synthesis, was used to arrest cell proliferation. After partially scraping out MCF7 cells from the cell culture dish, we monitored the movement of the remaining cells for the following 72 hrs. After 72 hrs, 10−6 and 10−5 M of RA significantly inhibited the migration of MCF7 cells towards the scraped area ‘the wound healing’ compared with control untreated cells (Fig.2A and B). It is important to note that the 60% of cell migration inhibition started from RA 10−6 M, but at the same concentration the cell viability was not affected (Figs1A and 2A, B). Similar results were obtained in T47D cellular line (data not shown).


Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta.

Flamini MI, Gauna GV, Sottile ML, Nadin BS, Sanchez AM, Vargas-Roig LM - J. Cell. Mol. Med. (2014)

(A) MCF7 cells were treated with retinoic acid (RA) in different concentrations (10−7/10−5 M) and cell migration was imaged after 72 hrs. (B) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. (C) T47D cells were treated with RA (10−6 M) and the synthetic agonist retinoids, selective for RARα Agonist (BMS753), RARβ Agonist (BMS453) and RARγ Agonist (BMS961), and the synthetic antagonist retinoids selective for RARα (BMS195614) plus RA (10−6 M). All retinoids were incubated at 10−6 M for 72 hrs. Cell migration was imaged after 72 hrs. (D) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. These experiments were performed in triplicates and representative images are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508151&req=5

fig02: (A) MCF7 cells were treated with retinoic acid (RA) in different concentrations (10−7/10−5 M) and cell migration was imaged after 72 hrs. (B) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. (C) T47D cells were treated with RA (10−6 M) and the synthetic agonist retinoids, selective for RARα Agonist (BMS753), RARβ Agonist (BMS453) and RARγ Agonist (BMS961), and the synthetic antagonist retinoids selective for RARα (BMS195614) plus RA (10−6 M). All retinoids were incubated at 10−6 M for 72 hrs. Cell migration was imaged after 72 hrs. (D) Gap closure was quantified with the use of NIH image J software. *P < 0.05 versus Con. These experiments were performed in triplicates and representative images are shown.
Mentions: The effect of RA on breast cancer cell migration was then tested in a dose–response experiment. To distinguish cell migration from cell proliferation, Cytosine-β-d-arabinofuranoside hydrochloride (10 μM), a selective inhibitor of DNA strand separation that does not block RNA synthesis, was used to arrest cell proliferation. After partially scraping out MCF7 cells from the cell culture dish, we monitored the movement of the remaining cells for the following 72 hrs. After 72 hrs, 10−6 and 10−5 M of RA significantly inhibited the migration of MCF7 cells towards the scraped area ‘the wound healing’ compared with control untreated cells (Fig.2A and B). It is important to note that the 60% of cell migration inhibition started from RA 10−6 M, but at the same concentration the cell viability was not affected (Figs1A and 2A, B). Similar results were obtained in T47D cellular line (data not shown).

Bottom Line: The retinoic acid receptor β (RARβ) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis.On the contrary, the addition of the selective retinoid RARβ-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition.When RARβ gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c-Src and FAK expressions.

View Article: PubMed Central - PubMed

Affiliation: Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentina, Mendoza, Argentina.

Show MeSH
Related in: MedlinePlus