So far, 3 isoforms have been identified. As SERCA serves to maintain the concentration gradient between find more the cytoplasm and the ER by pumping calcium into the ER, SERCA has been regarded as a potential mediator of alterations of the ER Ca2+-content. In heart failure, the ER Ca2+-content of cardiac GS-9973 purchase myocytes has been found to be reduced due to altered expression of SERCA [6]. In our laboratory, bronchial hyperreactivity in an asthma model was correlated with increased Ca2+-content in the sarcoplasmic reticulum of airway smooth muscle cells [4]. Further, in an interleukin based asthma model, the increased Ca2+-content was at least partially caused

by increased expression of SERCA [7]. Several studies investigated the expression of SERCA

in normal and tumor tissue reporting downregulation of this ATPase in cancer [8–11]. But, in colorectal cancer, Chung et al. reported that SERCA 2 mRNA was increased compared to normal tissue [12]. Moreover, increased SERCA 2 protein levels were correlated with serosal invasion, lymph node metastasis, advanced tumor stage and poorer survival-rate. Hence, an altered Ca2+-content of the ER might not only be involved in the early steps of carcinogenesis but may also cause further malignant transformation towards an invasive and aggressive phenotype. Investigating the correlation of SERCA expression, [Ca2+]ER and proliferation, Legrand et al. showed that in prostate cancer cells an increased growth rate was correlated with higher [Ca2+]ER and increased SERCA 2 expression [13]. A decreased growth rate was MK0683 in vivo correlated with decreased [Ca2+]ER and decreased expression of SERCA 2b. Neuroendocrine differentiation of prostate cAMP cancer cells is considered to mark increased aggressiveness of cancer growth. Vanverberghe et al. showed that neuroendocrine differentiation in these cells was associated with apoptosis resistance probably

due to decreased filling of the ER Ca2+-store caused by under-expression of SERCA 2 and calreticulin [14]. But, Crepin at al. reported that prolactin stimulated proliferation in immortalized prostate cells through increased [Ca2+]ER due to increased SERCA 2 expression [15]. In a comprehensive review, Lipskaia proposed that proliferation is associated with a sustained increase in [Ca2+]c or sustained Ca2+-oscillations, decreased refilling of the ER because of SERCA inhibition, and enhanced store operated Ca2+-entry from the extracellular space [16]. Apparently, the relationship between [Ca2+]ER, SERCA expression and tumor growth varies between studies, cell types and differentiation status. However, an altered ER Ca2+-homeostasis is obviously involved in malignant transformation. To our knowledge, this is the first report showing an altered ER Ca2+-homeostasis in lung cancer cells. The IP3R is a Ca2+-channel composed of 4 subunits, which releases calcium upon the binding of IP3 [17].