Endoplasmic reticulum calcium homeostasis is involved in a multitude of 
signaling, as well as "house-keeping" functions that control cell growth, 
differentiation or apoptosis in every human/eukaryotic cell. Calcium is actively 
accumulated in the endoplasmic reticulum by Sarco/Endoplasmic Reticulum Calcium 
transport ATPases (SERCA enzymes). SERCA-dependent calcium transport is the only 
calcium uptake mechanism in this organelle, and therefore the regulation of 
SERCA function by the cell constitutes a key mechanism to adjust calcium 
homeostasis in the endoplasmic reticulum depending on the cell type and its 
state of differentiation. The direct pharmacological modulation of SERCA 
activity affects cell differentiation and survival. SERCA expression levels can 
undergo significant changes during cell differentiation or tumorigenesis, 
leading to modified endoplasmic reticulum calcium storage. In several cell types 
such as cells of hematopoietic origin or various epithelial cells, two SERCA 
genes (SERCA2 and SERCA3) are simultaneously expressed. Expression levels of 
SERCA3, a lower calcium affinity calcium pump are highly variable. In several 
cell systems SERCA3 expression is selectively induced during differentiation, 
whereas during tumorigenesis and blastic transformation SERCA3 expression is 
decreased. These observations point at the existence of a cross-talk, via the 
regulation of SERCA3 levels, between endoplasmic reticulum calcium homeostasis 
and the control of cell differentiation, and show that endoplasmic reticulum 
calcium homeostasis itself can undergo remodeling during differentiation. The 
investigation of the anomalies of endoplasmic reticulum differentiation in tumor 
and leukemia cells may be useful for a better understanding of the contribution 
of calcium signaling to the establishment of malignant phenotypes.