Abstract
Cyclic AMP element modulator (CREM) is a transcription factor best known for its intricate involvement in spermatogenesis. The CREM gene encodes for multiple protein isoforms, which can enhance or repress transcription of target genes. Recent studies have identified fusion genes, with CREM as a partner gene in many neoplastic diseases. EWSR1-CREM fusion genes have been found in several mesenchymal tumors and in salivary gland carcinoma. These genes encode fusion proteins that include the C-terminal DNA-binding domain of CREM. We used a transcriptomic approach and immunohistochemistry to study the expression of CREM isoforms that include DNA-binding domains across human tissues. We found that CREM protein is widely expressed in almost all normal human tissues. A transcriptomic analysis of normal tissues and cancer showed that transcription of CREM can be altered in tumors, suggesting that also wild-type CREM may be involved in cancer biology. The wide expression of CREM protein in normal human tissues and cancer may limit the utility of immunohistochemistry for identification of tumors with CREM fusions:
Highlights
Cyclic AMP element modulator (CREM) is a transcriptional regulator protein that belongs to the cAMP response element–binding protein (CREB) transcription factor protein family
The cells had been treated with CREM-targeting small interfering RNA (siRNA) or control siRNA
We wanted to test whether the CREM antibody would detect an EWS RNA binding protein 1 (EWSR1)-CREM fusion in the CHL-1 cell line, which is known to harbor this rearrangement.[17]
Summary
Cyclic AMP element modulator (CREM) is a transcriptional regulator protein that belongs to the cAMP response element–binding protein (CREB) transcription factor protein family. This is a family of basic domain-leucine zipper proteins with a capacity to bind to the cAMP response element (CRE), which is a sequence present in the regulatory region of a large number of target genes.[1,2] The CREM gene has several promoters that give rise to multiple isoforms. Different isoforms of CREM can promote or repress expression from the CRE. It has been discovered to have a role in mediating impulsive behavior and addiction, as well as in regulating the spinal morphology and neuroplasticity.[6]
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More From: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
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