Activation of the ER stress and calcium signaling in angiomyolipoma

Rok, strany: 2016, 687 - 695

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. Keywords: angiomyolipoma, endoplasmic reticulum stress, inositol 1,4,5-trisphosphate receptors

ISO 690:

Novotna, B., Takacova, M., Hudecova, S., Lencesova, L., Breza, J., Misak, A., Csaderova, L., Pastoreková, S., Krizanova, O. 2016. Activation of the ER stress and calcium signaling in angiomyolipoma. In NEOPLASMA, vol. 63, no.5, pp. 687-695. 0028-2685.

APA:

Novotna, B., Takacova, M., Hudecova, S., Lencesova, L., Breza, J., Misak, A., Csaderova, L., Pastoreková, S., Krizanova, O. (2016). Activation of the ER stress and calcium signaling in angiomyolipoma. NEOPLASMA, 63(5), 687-695. 0028-2685.