TY - JOUR
T1 - PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression
AU - Uchi, Ryutaro
AU - Kogo, R.
AU - Kawahara, K.
AU - Sudo, T.
AU - Yokobori, T.
AU - Eguchi, H.
AU - Sugimachi, K.
AU - Maehama, T.
AU - Mori, Masaki
AU - Suzuki, A.
AU - Komune, S.
AU - Mimori, K.
N1 - Funding Information:
We thank T Shimooka and M Kasagi for their technical assistance. We also thank H Miyoshi (RIKEN BioResource Center) for providing lentivirus vector plasmid DNA, and Y Matsuzaki from the Laboratory for Technical Support, Medical Institute of Bioregulation, Kyushu University for her technical support for sequence analyses. This work was supported in part by the following grants and foundations: CREST; Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS); Grant-in-Aid for Scientific Research, grant numbers 20390360, 20591547, 20790960, 21591644, 21791295, 21791297, 215921014, and 21679006; the Funding Program for Next Generation World-Leading Researchers (LS094); and NEDO (New Energy and Industrial Technology Development Organization).
PY - 2013/10/15
Y1 - 2013/10/15
N2 - Background:The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.Methods:To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.Results:Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).Conclusion:The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
AB - Background:The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.Methods:To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.Results:Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).Conclusion:The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
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U2 - 10.1038/bjc.2013.561
DO - 10.1038/bjc.2013.561
M3 - Article
C2 - 24045667
AN - SCOPUS:84885920289
VL - 109
SP - 2199
EP - 2206
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -
