scholarly journals Induced Chromosomal Proximity and Gene Fusions in Prostate Cancer

Science ◽  
2009 ◽  
Vol 326 (5957) ◽  
pp. 1230-1230 ◽  
Author(s):  
Ram-Shankar Mani ◽  
Scott A. Tomlins ◽  
Kaitlin Callahan ◽  
Aparna Ghosh ◽  
Mukesh K. Nyati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Critical Role ◽  
Human Prostate ◽  
Gene Fusions ◽  
Dna Double Strand Breaks ◽  
Cell Type Specificity ◽  
Protein Coding ◽  
Subsequent Exposure

Gene fusions play a critical role in cancer progression. The mechanisms underlying their genesis and cell type specificity are not well understood. About 50% of human prostate cancers display a gene fusion involving the 5′ untranslated region of TMPRSS2, an androgen-regulated gene, and the protein-coding sequences of ERG, which encodes an erythroblast transformation–specific (ETS) transcription factor. By studying human prostate cancer cells with fluorescence in situ hybridization, we show that androgen signaling induces proximity of the TMPRSS2 and ERG genomic loci, both located on chromosome 21q22.2. Subsequent exposure of the cells to gamma irradiation, which causes DNA double-strand breaks, facilitates the formation of the TMPRSS2-ERG gene fusion. These results may help explain why TMPRSS2-ERG fusions are restricted to the prostate, which is dependent on androgen signaling.

Steroid hormones stimulate human prostate cancer progression and metastasis

2006 ◽  
Vol 118 (9) ◽  
pp. 2123-2131 ◽  
Author(s):  
William A. Ricke ◽  
Kenichiro Ishii ◽  
Emily A. Ricke ◽  
Jeff Simko ◽  
Yuzhuo Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Steroid Hormones ◽  
Cancer Progression ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression

scholarly journals FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells

2010 ◽  
Vol 30 (5) ◽  
pp. 1243-1253 ◽  
Author(s):  
Li Ni ◽  
Chun-Song Yang ◽  
Daniel Gioeli ◽  
Henry Frierson ◽  
David O. Toft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Feedback Loop ◽  
Critical Role ◽  
Prostate Cancer Cells ◽  
Androgen Receptor Signaling ◽  
Hsp90 Chaperone ◽  
Chaperone Complex ◽  
Androgen Binding

ABSTRACT Prostate cancer progression to the androgen-independent (AI) state involves acquisition of pathways that allow tumor growth under low-androgen conditions. We hypothesized that expression of molecular chaperones that modulate androgen binding to AR might be altered in prostate cancer and contribute to progression to the AI state. Here, we report that the Hsp90 cochaperone FKBP51 is upregulated in LAPC-4 AI tumors grown in castrated mice and describe a molecular mechanism by which FKBP51 regulates AR activity. Using recombinant proteins, we show that FKBP51 stimulates recruitment of the cochaperone p23 to the ATP-bound form of Hsp90, forming an FKBP51-Hsp90-p23 superchaperone complex. In cells, FKBP51 expression promotes superchaperone complex association with AR and increases the number of AR molecules that undergo androgen binding. FKBP51 stimulates androgen-dependent transcription and cell growth, and FKBP51 is part of a positive feedback loop that is regulated by AR and androgen. Finally, depleting FKBP51 levels by short hairpin RNA reduces the transcript levels of genes regulated by AR and androgen. Because the superchaperone complex plays a critical role in determining the ligand-binding competence and transcription function of AR, it provides an attractive target for inhibiting AR activity in prostate cancer cells.

scholarly journals Modeling human prostate cancer progression in vitro

2018 ◽  
Vol 40 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Teresa T Liu ◽  
Jonathan A Ewald ◽  
Emily A Ricke ◽  
Robert Bell ◽  
Colin Collins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Prostate ◽  
Molecular Characteristics ◽  
Prostate Cancer Progression ◽  
Altered Gene Expression ◽  
Unique Model ◽  
Altered Gene

Abstract Detailed mechanisms involved in prostate cancer (CaP) development and progression are not well understood. Current experimental models used to study CaP are not well suited to address this issue. Previously, we have described the hormonal progression of non-tumorigenic human prostate epithelial cells (BPH1) into malignant cells via tissue recombination. Here, we describe a method to derive human cell lines from distinct stages of CaP that parallel cellular, genetic and epigenetic changes found in patients with cancers. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. Using diverse analytical strategies, we show that the BCaP model reproduces molecular characteristics of CaP in human patients. Furthermore, we demonstrate that BCaP cells have altered gene expression of shared pathways with human and transgenic mouse CaP data, as well as, increasing genomic instability with TMPRSS2–ERG fusion in advanced tumor cells. Together, these cell lines represent a unique model of human CaP progression providing a novel tool that will allow the discovery and experimental validation of mechanisms regulating human CaP development and progression. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. The BCaP model reproduces molecular characteristics of prostate cancer. The cells have altered gene expression with TMPRSS2-ERG fusion representing a unique model for prostate cancer progression.

scholarly journals Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Atsushi Koizumi ◽  
Shintaro Narita ◽  
Hiroki Nakanishi ◽  
Masaki Ishikawa ◽  
Satoshi Eguchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Fatty Acyl ◽  
Human Prostate ◽  
Pathological Stage ◽  
Double Bonds ◽  
Prostate Hyperplasia ◽  
Cellular Processes ◽  
Acyl Chains ◽  
Phosphatidylinositol Phosphates

Abstract Phosphoinositides (PIPs) participate in many cellular processes, including cancer progression; however, the metabolic features of PIPs associated with prostate cancer (PCa) are unknown. We investigated PIPs profiles in PTEN-deficient prostate cancer cell lines, human prostate tissues obtained from patients with PCa and benign prostate hyperplasia (BPH) specimens using mass spectrometry. In immortalized normal human prostate PNT1B cells, PTEN deficiency increased phosphatidylinositol tris-phosphate (PIP3) and decreased phosphatidylinositol mono- and bis-phosphate (PIP1 and PIP2), consistent with PTEN’s functional role as a PI(3,4,5)P3 3-phosphatase. In human prostate tissues, levels of total (sum of all acyl variants) phosphatidylinositol (PI) and PIP1 in PCa were significantly higher than in BPH, whereas PIP2 and PIP3 contents were significantly lower than in BPH. PCa patients had significantly higher proportion of PI, PIP1, and PIP2 with 0–2 double bonds in acyl chains than BPH patients. In subgroup analyses based on PCa aggressiveness, mean total levels of PI with 0–2 double bonds in acyl chains were significantly higher in patients with pathological stage T3 than in those with pathological stage T2. These data indicate that alteration of PIPs level and the saturation of acyl chains may be associated with the development and aggressiveness of prostate cancer, although it is unknown whether this alteration is causative.

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

2007 ◽  
Vol 13 (20) ◽  
pp. 6040-6048 ◽  
Author(s):  
Ruoxiang Wang ◽  
Jianchun Xu ◽  
Nicola Mabjeesh ◽  
Guodong Zhu ◽  
Jianguang Zhou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression ◽  
Normal Prostate ◽  
Prostate Development

scholarly journals Withania somnifera targets interleukin-8 and cyclooxygenase-2 in human prostate cancer progression

2017 ◽  
Vol 5 (2) ◽  
pp. 75-83 ◽  
Author(s):  
Anand Setty Balakrishnan ◽  
Abel Arul Nathan ◽  
Mukesh Kumar ◽  
Sudhakar Ramamoorthy ◽  
Sathish Kumar Ramia Mothilal
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Withania Somnifera ◽  
Cyclooxygenase 2 ◽  
Interleukin 8 ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression
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