title: Inhibition of cytohesin-1 by siRNA leads to reduced IGFR signaling in prostate cancer.
abstract: To explore how cytohesin-1 (CYTH-1) small interfering RNA (siRNA) influences the insulin-like growth factor receptor (IGFR)-associated signal transduction in prostate cancer, we transfected human prostate cancer PC-3 cell lines with liposome-encapsulated CYTH-1 siRNA in serum-free medium and exposed the cells to 100 nM IGF-1. The mRNA and protein levels of the signal molecules involved in the IGFR signaling pathways were determined by real-time PCR and detected by Western blotting. The relative mRNA levels of CYTH-1, c-Myc, cyclinD1 and IGF-1R (CYTH-1 siRNA group vs scrambled siRNA group) were 0.26 vs 0.97, 0.34 vs 1.06, 0.10 vs 0.95, and 0.27 vs 0.41 (P < 0.05 for all), respectively. The relative protein levels of CYTH-1, pIGF-1R, pIRS1, pAkt1, pErk1, c-Myc, and cyclinD1 (CYTH-1 siRNA group vs scrambled siRNA group) were 0.10 vs 1.00 (30 min), 0.10 vs 0.98 (30 min), 0.04 vs 0.50 (30 min), 0.10 vs 1.00 (30 min), 0.10 vs 1.00 (30 min), 0.13 vs 0.85 (5 h), and 0.08 vs 0.80 (7 h), respectively. The tyrosine kinase activity of IGF-1R was associated with CYTH-1. The proliferative activity of PC-3 cells transfected with CYTH-1 siRNA was significantly lower than that of cells transfected with scrambled siRNA at 48 h (40.5 vs 87.6%, P < 0.05) and at 72 h (34.5 vs 93.5%, P < 0.05). In conclusion, the interference of siRNA with cytohesin-1 leads to reduced IGFR signaling in prostate cancer; therefore, CYTH-1 might serve as a new molecular target for the treatment of prostate cancer.
authors.affiliation: Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Weizhong
authors.forename: Gao
authors.initials: G
authors.lastname: Shuohui
authors.forename: Qin
authors.initials: Q
authors.lastname: Hanjiao
authors.forename: Man
authors.initials: M
authors.lastname: Yuhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiaohua
authors.forename: Cao
authors.initials: C
authors.lastname: Jian
authors.forename: Li
authors.initials: L
authors.lastname: Lisen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D017451:Receptors, Somatomedin; C100723:cytohesin-1; C102474:cytohesin-2; C040985:phosphatidylinositol receptors; D007334:Insulin-Like Growth Factor I