TY - JOUR
T1 - Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors
AU - Hsu, Kai Hsi
AU - Tsai, Hung Wen
AU - Lin, Pin Wen
AU - Hsu, Yun Shang
AU - Lu, Pei Jung
AU - Shan, Yan Shen
N1 - Funding Information:
This study is supported by the National Science Council, Taiwan, Grant NSC-98-2314-B001-MY2; Department of Health Grant DOH99-TD-C-111-003.
PY - 2014/6/20
Y1 - 2014/6/20
N2 - Background: Osteopontin (OPN) is a secreted phosphoprotein expressed by neoplastic cells involved in the malignant potential and aggressive phenotypes of human malignancies, including gastrointestinal stromal tumors (GISTs). Our previous study showed that OPN can promote tumor cell proliferation in GISTs. In this series, we further aim to investigate the effect of OPN on apoptosis in GISTs.Methods: The expression of apoptotic and anti-apoptotic proteins in response to OPN was evaluated. In vitro effects of OPN against apoptosis in GIST were also assessed. GIST specimens were also used for analyzing protein expression of specific apoptosis-related molecules and their clinicopathologic significance.Results: Up-regulation of β-catenin and anti-apoptotic proteins Mcl-1 with concomitant suppression of apoptotic proteins in response to OPN was noted. A significant anti-apoptotic effect of OPN on imatinib-induced apoptosis was identified. Furthermore, Mcl-1 overexpression was significantly associated with OPN and β-catenin expression in tumor tissues, as well as worse survival clinically.Conclusions: Our study identifies anti-apoptotic effects of OPN that, through β-catenin-mediated Mcl-1 up-regulation, significantly antagonized imatinib-induced apoptosis in GISTs. These results provide a potential rationale for therapeutic strategies targeting both OPN and Mcl-1 of the same anti-apoptotic signaling pathway, which may account for resistance to imatinib in GISTs.
AB - Background: Osteopontin (OPN) is a secreted phosphoprotein expressed by neoplastic cells involved in the malignant potential and aggressive phenotypes of human malignancies, including gastrointestinal stromal tumors (GISTs). Our previous study showed that OPN can promote tumor cell proliferation in GISTs. In this series, we further aim to investigate the effect of OPN on apoptosis in GISTs.Methods: The expression of apoptotic and anti-apoptotic proteins in response to OPN was evaluated. In vitro effects of OPN against apoptosis in GIST were also assessed. GIST specimens were also used for analyzing protein expression of specific apoptosis-related molecules and their clinicopathologic significance.Results: Up-regulation of β-catenin and anti-apoptotic proteins Mcl-1 with concomitant suppression of apoptotic proteins in response to OPN was noted. A significant anti-apoptotic effect of OPN on imatinib-induced apoptosis was identified. Furthermore, Mcl-1 overexpression was significantly associated with OPN and β-catenin expression in tumor tissues, as well as worse survival clinically.Conclusions: Our study identifies anti-apoptotic effects of OPN that, through β-catenin-mediated Mcl-1 up-regulation, significantly antagonized imatinib-induced apoptosis in GISTs. These results provide a potential rationale for therapeutic strategies targeting both OPN and Mcl-1 of the same anti-apoptotic signaling pathway, which may account for resistance to imatinib in GISTs.
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U2 - 10.1186/1477-7819-12-189
DO - 10.1186/1477-7819-12-189
M3 - Article
C2 - 24947165
AN - SCOPUS:84903730597
VL - 12
JO - World Journal of Surgical Oncology
JF - World Journal of Surgical Oncology
SN - 1477-7819
IS - 1
M1 - 189
ER -