Transcription Factor CREB is Involved in CaSR‐mediated Cytoskeleton Gene Expression

Abstract

Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca 21 ]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 [Ca 21 ]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca 21 ]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 [Ca 21 ]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 [Ca 21 ]i probably modulate cytoskeleton organization and gene expression via transcription factor CREB. Anat Rec, 298:501-512, 2015. V C 2014 Wiley Periodicals, Inc.

Decrease of phosphorylated proto-oncogeneCREBat Ser 133 site inhibits growth and metastatic activity of renal cell cancer

“…The constructions of Ser 133 mutant CREB recombination plasmids were finished according to the previous reports [22]. In brief, the CREB coding DNA sequence was amplified by the specific primers [23] and inserted into the EcoR I-Not I site of pCDH-Puro (vector) lentiviral expression vector. The dominant negative plasmid pCDH-CREB-PM-Puro was constructed with Thr instead of Ser 133 by the site-directed mutagenesis kit.…”

Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition

“…In response to various signals, on binding to the cAMP-responsive element (CRE) sequence (TGACGTCA), phosphorylation of CREB (pCREB) at the Ser133 residue is activated by a number of kinases (9). Activated CREB subsequently regulates various cell functions by enhancing the expression of target genes (10)(11)(12). Several studies have demonstrated that overexpression of pCREB promotes tumorigenesis in various cancer tissues, including acute myeloid leukemia (13,14), non-small cell lung carcinoma (15,16), breast (17,18), melanoma (19) and hepatocellular…”

The Transcription Factor Creb is Involved in Sorafenib-Inhibited Renal Cancer Cell Proliferation, Migration and Invasion

“…Nonetheless, the possible role of pCREB in the progression of sorafenib-treated RCC growth and metastasis has not been investigated. In this study, we used the recombinant plasmid pCI-neo/CREB (PN) (constitutively active CREB at Ser-133) (19) to investigate the role of CREB in sorafenib-treated RCC cell lines and demonstrate its effects on cell proliferation and migration under CREB signaling.…”