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FOR AUTHORS Neoplasma 2016 Neoplasma Vol.63, No.5, p.687-695,2016
FOR AUTHORS Neoplasma 2016 Neoplasma Vol.63, No.5, p.687-695,2016
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Neoplasma Vol.63, No.5, p.687-695,2016 |
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| Title: Activation of the ER stress and calcium signaling in angiomyolipoma | ||
| Author: B. NOVOTNA, M. TAKACOVA, S. HUDECOVA, L. LENCESOVA, J. BREZA JR., A. MISAK, L. CSADEROVA, S. PASTOREKOVA, O. KRIZANOVA, J. BREZA | ||
| Abstract: Renal angiomyolipomas (AMLs) are uncommon benign tumors that occur sporadically or as a part of tuberous sclerosis complex (TSC). Risk of life threatening hemorrhage is the main clinical concern. Although several evidences suggest that hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is crucial for these tumors, modulation of other metabolic pathways might affect tumor growth and progression. Therefore, we aimed to further characterize angiomyolipoma by TSC1/TSC2 expression, hypoxic status, expression of endoplasmic reticulum (ER) stress markers and calcium transport from the ER through the inositol 1,4,5-trisphosphate (IP3) receptors. Despite our expectations, angiomyolipoma were not hypoxic, as determined by absent expression of the carbonic anhydrase IX, which is a reliable marker of hypoxia. This was in accord with very low expression of TSC1 (that is associated with HIF activation) and a high expression of TSC2. Angiomyolipoma specimens also showed a significant upregulation of an anti-apoptotic marker Bcl2 when compared to healthy kidney tissue supporting the induction of pro-survival signaling. Moreover, angiomyolipoma specimens showed the overexpression of the ER stress markers XBP1, CHOP and ATF4 as well as of the mediators of calcium metabolism, namely the type 1 and 2, but not the type 3 IP3 receptors. These data suggest that the ER stress response, survival and calcium metabolism-related pathways but not hypoxia is an important component of the angiomyolipoma pathogenesis. |
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| Keywords: angiomyolipoma, endoplasmic reticulum stress, inositol 1,4,5-trisphosphate receptors | ||
| Published online: 09-Sep-2016 | ||
| Year: 2016, Volume: 63, Issue: 5 | Page From: 687, Page To: 695 | |
| doi:10.4149/neo_2016_505 |
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