Iglesias González Pablo A, Mori Consuelo, Valdivieso Ángel G, Santa Coloma Tomás A
Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina, Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina.
Biomolecules. 2025 May 13;15(5):711. doi: 10.3390/biom15050711.
(phorbol ester induced gene-1/G-protein Coupled Receptor Class C Group 5 Member A) was the first identified member of the orphan G protein-coupled receptor family GPRC5. Deregulation of its expression is associated with the development and progression of various types of tumours, particularly colon carcinoma. In this work, we study the effects of vitamin D (VD, cholecalciferol) and retinoic acid (RA) on mRNA expression in the colorectal cancer cell lines Caco-2 and T84. Both VD (10 µM) and all-trans retinoic acid (ATRA, atRA, RA) (10 µM) increased mRNA levels. Protein kinase C (PKC) inhibition with Gö6983 (10 µM) completely abolished the effects of VD and RA on expression. In parallel, VD and RA increased cytosolic and mitochondrial ROS levels (cROS and mtROS). However, the antioxidants NAC (10 mM) and MitoTEMPO (10 µM) raised gene expression levels in the presence of VD or RA, suggesting that elevated ROS may inhibit expression. In conclusion, both VD and RA stimulate expression. The mechanisms involve a common and essential PKC signalling pathway, as Gö6983 inhibited both VD- and RA-induced signalling.
（佛波酯诱导基因-1/G蛋白偶联受体C类第5组成员A）是孤儿G蛋白偶联受体家族GPRC5中首个被鉴定出的成员。其表达失调与各类肿瘤尤其是结肠癌的发生和发展相关。在本研究中，我们探究了维生素D（VD，胆钙化醇）和视黄酸（RA）对结肠癌细胞系Caco-2和T84中mRNA表达的影响。VD（10 μM）和全反式视黄酸（ATRA，atRA，RA）（10 μM）均提高了mRNA水平。用Gö6983（10 μM）抑制蛋白激酶C（PKC）可完全消除VD和RA对表达的影响。同时，VD和RA增加了胞质和线粒体活性氧水平（cROS和mtROS）。然而，抗氧化剂NAC（10 mM）和MitoTEMPO（10 μM）在VD或RA存在的情况下提高了基因表达水平，这表明升高的活性氧可能抑制表达。总之，VD和RA均刺激表达。其机制涉及一条共同且必需的PKC信号通路，因为Gö6983抑制了VD和RA诱导的信号传导。
