Transcription factor CREB is involved in CaSR-mediated cytoskeleton gene expression.
Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca2+]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca2+]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca2+]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant negative plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca2+]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca2+]i probably modulate cytoskeleton organization and gene expression via transcription factor.
Department of Medical School, Ningbo University, Ningbo, 315211, China; Department of the Center for Translational Medicine, The Affiliated Hospital, Ningbo University School of Medicine, Ningbo, 315020, China.
Shuaishuai
S
Huang
Yu
Y
Ren
Ping
P
Wang
Yanyuan
Y
Li
Xue
X
Wang
Haihui
H
Zhuang
Rong
R
Fang
Yuduo
Y
Wang
Ningsheng
N
Liu
Michael
M
Hehir
Jeff X
JX
Zhou
D020013:Calcium Signaling; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
C095550:CASR protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D044169:Receptors, Calcium-Sensing; D017239:Paclitaxel
CREB; CaSR; calcium; cytoskeleton; gene expression; tumorigenesis