Reference - Detail
| RRC ID | 35790 |
|---|---|
| Author | Uchi R, Kogo R, Kawahara K, Sudo T, Yokobori T, Eguchi H, Sugimachi K, Maehama T, Mori M, Suzuki A, Komune S, Mimori K. |
| Title | PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression. |
| Journal | Br J Cancer |
| Abstract |
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. |
| Volume | 109(8) |
| Pages | 2199-206 |
| Published | 2013-10-15 |
| DOI | 10.1038/bjc.2013.561 |
| PII | bjc2013561 |
| PMID | 24045667 |
| PMC | PMC3798961 |
| MeSH | Cell Nucleolus / genetics Cell Nucleolus / metabolism Disease Progression Humans Proto-Oncogene Proteins c-mdm2 / metabolism Ribosomal Proteins / genetics Ribosomal Proteins / metabolism* Signal Transduction Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Tumor Suppressor Protein p53 / biosynthesis Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / antagonists & inhibitors Tumor Suppressor Proteins / biosynthesis Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* |
| IF | 5.791 |
| Times Cited | 12 |
| WOS Category | ONCOLOGY |
| Resource | |
| DNA material | pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394). |