title: RNA interference-mediated knockdown of astrocyte elevated gene-1 inhibits growth, induces apoptosis, and increases the chemosensitivity to 5-fluorouracil in renal cancer Caki-1 cells.
abstract: Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the anti-apoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Shan
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The Second Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Song
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins; D034622:RNA Interference; D016601:RNA-Binding Proteins
chemical_list: D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D005472:Fluorouracil
keywords: apoptosis; astrocyte elevated gene-1; chemosensitivity; proliferation; renal cancer cells