Izquierdo-Torres Eduardo, Rodríguez Gabriela, Meneses-Morales Iván, Zarain-Herzberg Angel
Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Mol Carcinog. 2017 Jul;56(7):1703-1711. doi: 10.1002/mc.22625. Epub 2017 Feb 15.
The Ca -ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca ] homeostasis by pumping Ca into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate. Resveratrol (RSV), a phytoalexin produced by a wide variety of plants in response to stress situations can modulate cellular processes involved in all stages of carcinogenesis. In this work, we used breast cancer cell lines (MCF-7 and MDA-MB-231) to evaluate mRNA levels of ATP2A2 and ATP2A3 genes in response to RSV treatment. Our results demonstrate that RSV treatment induced the expression of ATP2A3 gene in both cell lines in a time and concentration-dependent manner, while the expression of ATP2A2 gene remained unaffected. The RSV-induced expression of SERCA3 in these breast cancer cell lines produced decreased cell viability, triggered apoptosis and changes in cytosolic Ca levels, as well as changes in the capacity for Ca release by the ER. These data suggest an important participation of SERCA3 genes in RSV-mediated anti-tumor effect in breast cancer cell lines. Nevertheless, further research is needed to elucidate the molecular mechanisms underlying this effect.
肌浆网/内质网（SERCA）的钙 -ATP酶对于通过将钙泵入真核细胞的内质网（ER）来维持细胞内[Ca]稳态至关重要。SERCA酶由三个不同的基因（ATP2A1 - 3）编码，其表达以组织和发育阶段特异性的方式发生。据报道，在不同类型的癌症中，如口腔癌、肺癌、结肠癌、胃癌、中枢神经系统癌、甲状腺癌、乳腺癌和前列腺癌，SERCA2和SERCA3泵的表达发生了改变。白藜芦醇（RSV）是多种植物在应激情况下产生的一种植保素，它可以调节参与致癌作用各个阶段的细胞过程。在这项工作中，我们使用乳腺癌细胞系（MCF - 7和MDA - MB - 231）来评估ATP2A2和ATP2A3基因在RSV处理后的mRNA水平。我们的结果表明，RSV处理以时间和浓度依赖性方式诱导了这两种细胞系中ATP2A3基因的表达，而ATP2A2基因的表达保持不变。RSV诱导的这些乳腺癌细胞系中SERCA3的表达导致细胞活力下降、引发细胞凋亡和胞质钙水平变化，以及内质网钙释放能力的变化。这些数据表明SERCA3基因在RSV介导的乳腺癌细胞系抗肿瘤作用中起重要作用。然而，需要进一步研究来阐明这种作用背后的分子机制。
