TY - JOUR
T1 - Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis
AU - Nakanishi, Yutaka
AU - Shiraha, Hidenori
AU - Nishina, Shin ichi
AU - Tanaka, Shigetomi
AU - Matsubara, Minoru
AU - Horiguchi, Shigeru
AU - Iwamuro, Masaya
AU - Takaoka, Nobuyuki
AU - Uemura, Masayuki
AU - Kuwaki, Kenji
AU - Hagihara, Hiroaki
AU - Toshimori, Junichi
AU - Ohnishi, Hideki
AU - Takaki, Akinobu
AU - Nakamura, Shinichiro
AU - Kobayashi, Yoshiyuki
AU - Nouso, Kazuhiro
AU - Yagi, Takahito
AU - Yamamoto, Kazuhide
N1 - Funding Information:
This work was supported by USPHS/NIH grants 5R01CA058443 and 5R01CA105257 (to SAN). AMQ was partially supported by grant 5F31HL090024. ChIP on chip assays were performed at the Keck-UNM genomics facility funded by a grant from the W. M. Keck Foundation with additional funding from the State of New Mexico and the University of New Mexico Cancer Center. Some of these experiments used the Shared Flow Cytometry Resource in the UNM Cancer Center. The authors thank Julie Torres and John-Michael Thomas for expert technical assistance and Dr. Tom Gonda and Dr. Bruce Bunnell for providing lentivirus vectors. The authors report no conflicts of interest. Affymetrix tiling array ChIP on chip data has been deposited in the NCBI GEO database [GEO:GSE18706].
PY - 2011/1/4
Y1 - 2011/1/4
N2 - Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
AB - Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
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U2 - 10.1186/1471-2407-11-30
DO - 10.1186/1471-2407-11-30
M3 - Article
C2 - 21205319
AN - SCOPUS:78650761959
SN - 1471-2407
VL - 11
JO - BMC Cancer
JF - BMC Cancer
M1 - 3
ER -
