Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

Liu, Jun-Bao,Dai, Chun-Mei,Su, Xiao-Yun,Cao, Lu,Qin, Rui,Kong, Qing-Bo Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

Anti-androgen-independent Prostate Cancer Effects of Ginsenoside Metabolites In Vitro: Mechanism and Possible Structure-Activity Relationship Investigation

Wei Li,Yong Liu,Jiang-Wei Zhang,Chun-Zhi Ai,Nan Xiang,Hui-Xin Liu,Ling Yang 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

Treatment of androgen-independent prostate cancer (AIPC) remains unsatisfactory. In our present experiment, natural occurring ginsenosides (NOGs) and intestinal bacterial metabolites (IBMs) were employed to investigate their anti-AIPC cell growth activity using PC-3 cells. Our results showed that the IBMs exerted more portent anti-AIPC activity than NOGs, by decreasing survival rate, inhibiting proliferation, inducing apoptosis, and leading to cell cycle arrest in AIPC PC-3 cells. The increase of LogP and decrease of C-6 steric hindrance, which were caused by deglycosylation by intestinal bacteria, may be the reason for the higher anti-AIPC activity of IBMs.

인간의 전립선암세포주인 DU145 세포와 단핵구인 THP-1 세포의 상호작용이 종양 증식에 미치는 영향

임도영,조한진,김종대,윤정한 대한암예방학회 2011 Journal of cancer prevention Vol.16 No.3

Tumor and tumor-microenvironment are most important aspects in recent years. Tumor associated macrophages (TAM) play key roles in tumor-microenvironment. Macrophages are originated from blood monocytes. In this study, we examined whether DU145 androgen-independent prostate cancer cells and THP-1 human monocytes interact each other in vivo and in vitro. In vivo xenograft model, DU145 cells and/or THP-1 cells were inoculated subcutaneously in Balb/c nude mice. Tumor growth was accelerated in a group of co-inoculation of DU145 cells with THP-1 cells compared to only DU145 or THP-1cell-injected group. Immunohistochemistry assay in tumors revealed that Ki67, CD31, and vascular endothelial growth factor (VEGF) expressions were increased by the co-inoculation group. Secretion of IL-6, IL-8 or VEGF were induced when DU145 cells incubated with THP-1 cells. In the present study,we demonstrated that increase of IL-6, IL-8 and VEGF secretion in co-culture of DU145 and THP-1cells may one of the key inducers of promotion in tumor growth of co-inoculation with DU145 human prostate cancer cells and THP-1 human monocytes. (Cancer Prev Res 16, 194-199, 2011)

Insulin-Like Growth Factor-I Induces Androgen Receptor Activation in Differentiating C2C12 Skeletal Muscle Cells

Hye Jin Kim,이원준 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.3

The modulating effect of IGF-I on the regulation of AR gene expression and activation in skeletal muscle cells remains poorly understood. In this study, the effects of IGF-I treatment on AR induction and activation in the absence of AR ligands were examined. Differentiating C2C12 cells were treated with different concentrations (0-250 ng/ml) of IGF-I or for various periods of time (0-60 min) of 250 ng/ml IGF-I. Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent increase in total AR and phosphorylated AR (Ser 213). IGF-I treatment also led to significantly increased AR mRNA expression when compared with the control. The levels of skeletal α-actin and myogenin mRNA, known target genes of AR, were also significantly upregulated after 5 or 10 min of treatment with IGF-I. Confocal images revealed that IGF-I stimulated nuclear localization of AR in the absence of ligands. In addition, an electrophoretic mobility shift assay indicated that IGF-I stimulated the AR DNA binding activity in a time-dependent manner. The present results suggest that IGF-I stimulates the expression and activation of AR by ligand-independent mechanism in differentiating C2C12 mouse skeletal muscle cells

Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells

이원준 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.5

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal α-actin mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

Ligand-Independent Activation of the Androgen Receptor by Insulin-Like Growth Factor-I and the Role of the MAPK Pathway in Skeletal Muscle Cells

Hye Jin Kim,이원준 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.6

In this study, the roles of the p38 MAPK, ERK1/2 and JNK signaling pathway in IGF-I-induced AR induction and activa-tion were examined. C2C12 cells were treated with IGF-I in the absence or presence of various inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), and JNK (SP600125). Inhibi-tion of the MAPK pathway with SB203580, PD98059, or SP600125 significantly decreased IGF-I-induced AR pho-sphorylation and total AR protein expression. IGF-I-induced nuclear fraction of total AR and phosphorylated AR were significantly inhibited by SB203580, PD98059, or SP600125. Furthermore, IGF-I-induced AR mRNA and skeletal -actin mRNA were blocked by those inhibitors in dose-dependent manner. Confocal images showed that IGF-I-induced AR nuclear translocation from cytosol was significantly blocked by SB203580, PD98059, or SP600125, suggesting that the MAPK pathway regulates IGF-I-induced AR nuclear localiza-tion in skeletal muscle cells. The present results suggest that the MAPK pathways are required for the ligand-independent activation of AR by IGF-I in C2C12 skeletal muscle cells.