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FAM9C plays an anti-apoptotic role through activation of the PI3K/Akt pathway in human hepatocellular carcinoma
- Source :
- Oncology reports. 30(3)
- Publication Year :
- 2013
-
Abstract
- The function of FAM9C encoding a testis-exclusively expressed and nuclear-localized protein remains unknown. In the present study, we evaluated the role of FAM9C in human hepatocellular carcinoma. We found that among three FAM9 family members, only FAM9C was frequently upregulated in HCC specimens compared with that in corresponding adjacent non-cancer liver tissues. FAM9C was located in the nucleus of HCC cells, as shown by both western blotting and immumofluorescence assays. Significantly, FAM9C overexpression promoted proliferation, clonogenicity in an anchorage-dependent manner, in vivo tumorigenicity of YY-8103, and Huh-7 cells. In contrast, FAM9C knockdown suppressed proliferation, anchorage-dependent colony formation and in vivo tumorigenicity of QGY-7703, and BEL-7404 cells. However, FAM9C had no significant effects on cell cycle progression when FAM9C was stably overexpressed in Huh-7 cells or knocked down in BEL-7404 cells. Most importantly, FAM9C regulated activation of Akt and UV-induced apoptosis in HCC cells. FAM9C overexpression increased the phosphorylation levels of Akt and anti-apoptotic ability of Huh-7 cells, whereas endogenous FAM9C knockdown reduced the phosphorylated levels of Akt and anti-apoptotic ability of BEL-7404 cells. Furthermore, the anti-apoptotic function of FAM9C could be prevented when the PI3K-Akt pathway was in a loss-of-function caused by RNA interference against Akt or PI3K inhibitor LY294002 in HCC cells. Taken together, our data demonstrate that FAM9C as a novel cancer testis gene plays an anti-apoptotic role in human hepatocellular carcinoma through activating the PI3K/Akt signaling pathway, and serves as a promising target for HCC therapy.
- Subjects :
- Cancer Research
Carcinoma, Hepatocellular
Cell
Blotting, Western
Fluorescent Antibody Technique
Mice, Nude
Apoptosis
Biology
Real-Time Polymerase Chain Reaction
Immunoenzyme Techniques
Mice
Phosphatidylinositol 3-Kinases
medicine
Tumor Cells, Cultured
Animals
Humans
RNA, Messenger
Phosphorylation
RNA, Small Interfering
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
Oncogene
Akt/PKB signaling pathway
Reverse Transcriptase Polymerase Chain Reaction
Liver Neoplasms
Nuclear Proteins
General Medicine
Cell cycle
Flow Cytometry
Xenograft Model Antitumor Assays
digestive system diseases
medicine.anatomical_structure
Oncology
Cancer research
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 17912431
- Volume :
- 30
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Oncology reports
- Accession number :
- edsair.doi.dedup.....eca23b0bd6bc9f0f0df30b19e6f3d5fb