التفاصيل البيبلوغرافية
| العنوان: |
Silencing Mutated β-Catenin Inhibits Cell Proliferation and Stimulates Apoptosis in the Adrenocortical Cancer Cell Line H295R. |
| المؤلفون: |
Gaujoux, Sébastien, Hantel, Constanze, Launay, Pierre, Bonnet, Stéphane, Perlemoine, Karine, Lefèvre, Lucile, Guillaud-Bataille, Marine, Beuschlein, Felix, Tissier, Frédérique, Bertherat, Jérôme, Rizk-Rabin, Marthe, Ragazzon, Bruno |
| المصدر: |
PLoS ONE; Feb2013, Vol. 8 Issue 2, p1-5, 5p |
| مصطلحات موضوعية: |
GENE silencing, CATENINS, INHIBITION of cellular proliferation, APOPTOSIS, ADRENOCORTICAL hormones, CANCER cell culture, ENDOCRINE gland tumors, HEALTH outcome assessment, SOMATIC mutation, TUMOR treatment |
| مستخلص: |
Context: Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating β-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target. Objective: Similar to patient tumor specimen the H295 cell line derived from an ACC harbors a natural activating β-catenin mutation. We herein assess the in vitro and in vivo effect of β-catenin inactivation using a doxycyclin (dox) inducible shRNA plasmid in H295R adrenocortical cancer cells line (clone named shβ). Results: Following dox treatment a profound reduction in β-catenin expression was detectable in shβ clones in comparison to control clones (Ctr). Accordingly, we observed a decrease in Wnt/βcatenin-dependent luciferase reporter activity as well as a decreased expression of AXIN2 representing an endogenous β-catenin target gene. Concomitantly, β-catenin silencing resulted in a decreased cell proliferation, cell cycle alterations with cell accumulation in the G1 phase and increased apoptosis in vitro. In vivo, on established tumor xenografts in athymic nude mice, 9 days of β-catenin silencing resulted in a significant reduction of CTNNB1 and AXIN2 expression. Moreover, continous β-catenin silencing, starting 3 days after tumor cell inoculation, was associated with a complete absence of tumor growth in the shβ group while tumors were present in all animals of the control group. Conclusion: In summary, these experiments provide evidences that Wnt/β-catenin pathway inhibition in ACC is a promising therapeutic target. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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