Disease relevance of CACNA2D2

• The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus, CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome [1].
• Expression deficiency of the CACNA2D2 in cancer cells suggests a possible link of it to Ca(2+) signaling in the pathogenesis of lung cancer and other cancers [2].

High impact information on CACNA2D2

• CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers [3].
• Because of its chromosomal location and expression patterns, CACNA2D2 needs to be explored as a potential tumor suppressor gene linking Ca(2+) signaling and lung, breast, and other cancer pathogenesis [1].
• Precise mapping of 15 independent HDs in the LUCA region allowed us to establish the smallest HD region in 3p21.3C located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene) [4].
• Overexpression of CACNA2D2 induced apoptosis in H1299 (12.5%), H358 (13.7%), H460 (22.3%), and A549 (50.1%) cell lines [2].
• Mitochondria membrane depolarization was observed prior to apoptosis in Ad-CACNA2D2 and Adp53-transduced H460 and A549 cells [2].

Biological context of CACNA2D2

• Exogenous expression of CACNA2D2 significantly inhibited tumor cell growth compared with the controls [2].
• CACNA2D2-mediated apoptosis in NSCLC cells is associated with alterations of the intracellular calcium signaling and disruption of mitochondria membrane integrity [2].
• We investigated the effects of overexpression of CACNA2D2 on intracellular Ca(2+) contents, mitochondria homeostasis, cell proliferation, and apoptosis by adenoviral vector-mediated wild-type CACNA2D2 gene transfer in 3p21.3-deficient nonsmall cell lung cancer cell lines [2].
• A G-to-A single nucleotide polymorphism in intron 2 of the human CACNA2D2 gene that maps at 3p21.3 [5].

Associations of CACNA2D2 with chemical compounds

• Together, these results suggest that one of the pathways in CACNA2D2-induced apoptosis is mediated through disruption of mitochondria membrane integrity, the release of cyt c, and the activation of caspases, a process that is associated with regulation of cytosolic free Ca(2+) contents [2].

References