Does constitutive calcium signaling stimulate proliferation at later stages of APA development?

Ascertain whether constitutive activation of calcium signaling in aldosterone-producing adenoma cells stimulates adrenocortical cell proliferation during later stages of adenoma development.

Background

The authors’ chemogenetic model shows that sodium entry and resultant calcium signaling increase aldosterone biosynthesis but reduce cell proliferation and increase apoptosis over 72 hours. However, clinical observations have linked KCNJ5-mutated APAs with larger tumor size and higher Ki67 in some studies, suggesting possible stage-dependent effects.

This raises the unresolved possibility that sustained calcium signaling might be proliferative at different phases of tumor evolution. Establishing whether such a temporal shift occurs would reconcile experimental and clinical data and refine models of APA progression.