TY - JOUR
T1 - Transcriptional regulation of adrenomedullin by oncostatin M in human astroglioma cells
T2 - Implications for tumor invasion and migration
AU - Lim, Seul Ye
AU - Ahn, So Hee
AU - Park, Hyunju
AU - Lee, Jungsul
AU - Choi, Kyungsun
AU - Choi, Chulhee
AU - Choi, Ji Ha
AU - Park, Eun Mi
AU - Choi, Youn Hee
N1 - Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) Grant 2012R1A5A2A32671866 and by NRF-2013R1A1A3009978.
PY - 2014
Y1 - 2014
N2 - Adrenomedullin (ADM), a secretory peptide with multiple functions in physiological to pathological conditions, is upregulated in several human cancers, including brain, breast, colon, prostate, and lung cancer. However, the molecular mechanisms underlying the regulation of ADM expression in cancerous cells are not fully understood. Here, we report that oncostatin M (OSM), a cytokine belonging to the interleukin-6 family, induces ADM expression in astroglioma cells through induction of signal transducer and activator of transcription-3 (STAT-3) phosphorylation, nuclear translocation, and subsequent DNA binding to the ADM promoter. STAT-3 knockdown decreased OSM-mediated expression of ADM, indicating that ADM expression is regulated by STAT-3 in astroglioma cells. Lastly, scratch wound healing assay showed that astroglioma cell migration was significantly enhanced by ADM peptides. These data suggest that aberrant activation of STAT-3, which is observed in malignant brain tumors, may function as one of the key regulators for ADM expression and glioma invasion.
AB - Adrenomedullin (ADM), a secretory peptide with multiple functions in physiological to pathological conditions, is upregulated in several human cancers, including brain, breast, colon, prostate, and lung cancer. However, the molecular mechanisms underlying the regulation of ADM expression in cancerous cells are not fully understood. Here, we report that oncostatin M (OSM), a cytokine belonging to the interleukin-6 family, induces ADM expression in astroglioma cells through induction of signal transducer and activator of transcription-3 (STAT-3) phosphorylation, nuclear translocation, and subsequent DNA binding to the ADM promoter. STAT-3 knockdown decreased OSM-mediated expression of ADM, indicating that ADM expression is regulated by STAT-3 in astroglioma cells. Lastly, scratch wound healing assay showed that astroglioma cell migration was significantly enhanced by ADM peptides. These data suggest that aberrant activation of STAT-3, which is observed in malignant brain tumors, may function as one of the key regulators for ADM expression and glioma invasion.
UR - http://www.scopus.com/inward/record.url?scp=84923351300&partnerID=8YFLogxK
U2 - 10.1038/srep06444
DO - 10.1038/srep06444
M3 - Article
C2 - 25246098
AN - SCOPUS:84923351300
SN - 2045-2322
VL - 4
JO - Scientific Reports
JF - Scientific Reports
M1 - 6444
ER -