論文 - 詳細
| RRC ID | 41614 |
|---|---|
| 著者 | Sasaki T, Fujimoto Y, Tsuchida A, Kawasaki Y, Kuwada Y, Chayama K. |
| タイトル | Activation of peroxisome proliferator-activated receptor gamma inhibits the growth of human pancreatic cancer. |
| ジャーナル | Pathobiology |
| Abstract |
OBJECTIVE:In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth. METHODS:Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays. RESULTS:PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth. CONCLUSION:These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer. |
| 巻・号 | 69(5) |
| ページ | 258-65 |
| 公開日 | 2001-1-1 |
| DOI | 10.1159/000064336 |
| PII | pat69258 |
| PMID | 12107343 |
| MeSH | Antineoplastic Agents / pharmacology Cell Division / drug effects Chromans / pharmacology Dose-Response Relationship, Drug Electrophoretic Mobility Shift Assay Humans Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology RNA, Messenger / metabolism RNA, Neoplasm / analysis Receptors, Cytoplasmic and Nuclear / biosynthesis* Receptors, Cytoplasmic and Nuclear / genetics Reverse Transcriptase Polymerase Chain Reaction Rosiglitazone Thiazoles / pharmacology Thiazolidinediones* Transcription Factors / biosynthesis* Transcription Factors / genetics Troglitazone Tumor Cells, Cultured / drug effects |
| IF | 1.985 |
| 引用数 | 13 |
| WOS 分野 | PATHOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |