1. Leucine-rich protein 130 contributes to apoptosis resistance of human hepatocarcinoma cells.
- Author
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Michaud M, Barakat S, Magnard S, Rigal D, and Baggetto LG
- Subjects
- Antibiotics, Antineoplastic pharmacokinetics, Antibiotics, Antineoplastic pharmacology, Apoptosis genetics, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Cell Line, Tumor, Daunorubicin pharmacokinetics, Daunorubicin pharmacology, Down-Regulation, Drug Resistance, Neoplasm, Genetic Vectors, Hep G2 Cells, Humans, Lentivirus genetics, Liver Neoplasms genetics, Liver Neoplasms metabolism, Microscopy, Fluorescence, Neoplasm Proteins genetics, RNA Interference, RNA, Small Interfering administration & dosage, RNA, Small Interfering genetics, Transfection, Apoptosis drug effects, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Neoplasm Proteins metabolism
- Abstract
LRP130 is a ubiquitous protein involved in cellular homeostasis, microtubule alteration, and transactivation of a few multidrug resistance genes. Its role in resistance to apoptosis in HepG2 and HUH7 hepatocarcinoma cells was investigated. Using shRNA-producing lentiviruses to down-regulate the LRP130 gene, we showed that i) LRP130 did not affect the capacity of hepatocarcinoma cells to extrude drugs since LRP130 down-regulation was insufficient to significantly reduce P-glycoprotein production in these cells, and ii) the expression of 11 apoptosis-related genes measured by PCR-array was significantly reduced. Interestingly, six of these genes encode extrinsic pathway proapoptotic proteins whose expression was higher in LRP130-non producing than in LRP130-producing HepG2 cells. Fluorescence microscopy confirmed this new anti-apoptotic role of LRP130, which is strengthened by a significantly reduced cytochrome c oxidase activity in LRP130-down-regulated hepatocarcinoma cells.
- Published
- 2011