التفاصيل البيبلوغرافية
| العنوان: |
Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathway. |
| المؤلفون: |
Ming‑Cheng Chang, Chi‑An Chen, Chang‑Yao Hsieh, Chien‑Nan Lee, Yi‑Ning Su, Yu‑Hao Hu |
| المصدر: |
Biochemical Journal; Dec2009, Vol. 424 Issue 3, p449-448, 0p |
| مصطلحات موضوعية: |
PACLITAXEL, APOPTOSIS, PROTEINS, REVERSE transcriptase polymerase chain reaction, CELL death, TARGETED drug delivery, DRUG resistance in cancer cells, CELLULAR signal transduction |
| مستخلص: |
Mesothelin, a secreted protein, is overexpressed in some cancers, but its exact function remains unclear. The aim of the present study was to evaluate the possible function of mesothelin. Real-time PCR, RT (reverse transcription)–PCR, cytotoxicity assays, proliferative assays, apoptotic assays by Hoechst staining, detection of active caspases 3 and 7 by flow cytometric analysis, and immunoprecipitation and immunoblotting were performed. Cancer tissues in paclitaxel-resistant ovarian cancer patients expressed higher levels of mesothelin as assessed using real-time PCR than paclitaxel-sensitive ovarian cancer patients (the mean crossing point value change of mesothelin was 26.9±0.4 in the resistant group and 34.3±0.7 for the sensitive group; P<0.001). Mesothelin also protected cells from paclitaxel-induced apoptosis. The protein expression of Bcl-2 family members, such as Bcl-2 and Mcl-1, was significantly increased regardless of whether cells were treated with exogenous mesothelin or were mesothelin-transfectants. Furthermore, mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) 1/2 for enhancing MAPK (mitogen-activated protein kinase) activity. The anti-apoptotic ability was suppressed and the expression of Bcl-2 family in response to mesothelin was altered by inhibiting PI3K activity, but not by inhibiting MAPK activity. Thus mesothelin can inhibit paclitaxel-induced cell death mainly by involving PI3K signalling in the regulation of Bcl-2 family expression. Mesothelin is a potential target in reducing resistance to cytotoxic drugs. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
