Methylation status of uPA promoter as a molecular mechanism regulating prostate cancer invasion and growth in vitro and in vivo

2003 ◽  
Vol 17 (9) ◽  
pp. 1081-1088 ◽  
Author(s):  
POUYA PAKNESHAN ◽  
ROSIE HONGMEI XING ◽  
SHAFAAT A. RABBANI
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanism ◽  
Methylation Status ◽  
Cancer Invasion

scholarly journals Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells

2007 ◽  
Vol 14 (3) ◽  
pp. 531-547 ◽  
Author(s):  
Ta-Chun Yuan ◽  
Suresh Veeramani ◽  
Ming-Fong Lin
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanism ◽  
Biochemical Properties ◽  
Normal Prostate ◽  
Independent State ◽  
Epithelial Compartment ◽  
Neuroendocrine Transdifferentiation ◽  
A Minor

Neuroendocrine (NE) cells represent a minor cell population in the epithelial compartment of normal prostate glands and may play a role in regulating the growth and differentiation of normal prostate epithelia. In prostate tumor lesions, the population of NE-like cells, i.e., cells exhibiting NE phenotypes and expressing NE markers, is increased that correlates with tumor progression, poor prognosis, and the androgen-independent state. However, the origin of those NE-like cells in prostate cancer (PCa) lesions and the underlying molecular mechanism of enrichment remain an enigma. In this review, we focus on discussing the distinction between NE-like PCa and normal NE cells, the potential origin of NE-like PCa cells, and in vitro and in vivo studies related to the molecular mechanism of NE transdifferentiation of PCa cells. The data together suggest that PCa cells undergo a transdifferentiation process to become NE-like cells, which acquire the NE phenotype and express NE markers. Thus, we propose that those NE-like cells in PCa lesions were originated from cancerous epithelial cells, but not from normal NE cells, and should be defined as ‘NE-like PCa cells’. We further describe the biochemical properties of newly established, stable NE-like lymph node carcinoma of the prostate (LNCaP) cell lines, transdifferentiated from androgen-sensitive LNCaP cells under androgen-deprived conditions. Knowledge of understanding NE-like PCa cells will help us to explore new therapeutic strategies for treating PCa.

scholarly journals SKI-606 (Bosutinib) Blocks Prostate Cancer Invasion, Growth, and Metastasis In vitro and In vivo through Regulation of Genes Involved in Cancer Growth and Skeletal Metastasis

2010 ◽  
Vol 9 (5) ◽  
pp. 1147-1157 ◽  
Author(s):  
Shafaat A. Rabbani ◽  
Maria-Luisa Valentino ◽  
Ani Arakelian ◽  
Suhad Ali ◽  
Frank Boschelli
Keyword(s):  
Prostate Cancer ◽  
Skeletal Metastasis ◽  
Cancer Invasion ◽  
Cancer Growth

scholarly journals LRP 5 knockdown: effect on prostate cancer invasion growth and skeletal metastasis in vitro and in vivo

2013 ◽  
Vol 2 (5) ◽  
pp. 625-635 ◽  
Author(s):  
Shafaat A. Rabbani ◽  
Ani Arakelian ◽  
Riaz Farookhi
Keyword(s):  
Prostate Cancer ◽  
Skeletal Metastasis ◽  
Cancer Invasion ◽  
Knockdown Effect

scholarly journals SOX9 in prostate cancer is upregulated by cancer-associated fibroblasts to promote tumor progression through HGF/c-Met-FRA1 signaling

2020 ◽  
Author(s):  
Haixiang Qin ◽  
Yang Yang ◽  
Bo Jiang ◽  
Chun Pan ◽  
Wei Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Molecular Mechanism ◽  
The Cancer Genome Atlas ◽  
Cancer Associated Fibroblasts ◽  
Sox9 Expression ◽  
In Vivo Experiments ◽  
Vitro Model

Abstract Background Previous studies have demonstrated that transcription factor SOX9 which was reactivated in prostate cancer (Pca) and promoted tumor growth was a poor prognostic biomarker for Pca. Nevertheless, the regulatory mechanism underlying SOX9 upregulation in Pca still remains unclear. Several cytokines widely distributed in the tumor microenvironment (TME) have been reported to be involved in the regulation of SOX9, suggesting that cancer-associated fibroblasts (CAFs), one of the main sources of secreted factors in TME, may play a role in regulating SOX9 expression. Methods Herein, an in vitro model of paracrine interaction between primary CAFs and Pca cells (both AR-positive and AR-negative Pca cells), was applied to investigate the molecular mechanism of SOX9 upregulation during Pca progression. The regulatory axis was validated by in vivo experiments and The Cancer Genome Atlas (TCGA) data. Results Conditional medium from Pca CAFs (CAF-CM) upregulated the expression of SOX9, which was also proved to be essential for CAF-induced tumor progression. Further analysis showed that it was hepatocyte growth factor (HGF) secreted by CAFs that was responsible for the SOX9 elevation in Pca cells via activating c-Met signaling. Mechanistically, HGF/c-Met signaling specifically activated MEK1/2-ERK1/2 pathway which then induced phosphorylated status and protein upregulation of FRA1. Furthermore, ChIP assay demonstrated that FRA1 transcriptionally upregulated SOX9 expression by binding to the TPA-responsive element (TRE) sequence in the promoter of SOX9 gene. We also found that HGF/c-Met-ERK1/2-FRA1-SOX9 axis was relatively conserved in human and mouse species by validating in mouse Pca cells (RM-1). Conclusions Our results revealed a novel insight into the molecular mechanism that SOX9 expression in Pca cells is promoted by CAFs, through the HGF/cMet-ERK1/2-FRA1 axis. Besides, SOX9 may serve as an alternative marker for the activated HGF/c-Met signaling to enroll the optimal Pca patients for HGF/c-Met inhibition treatment, since it is much more stable and easier to detect.

scholarly journals Upregulated PPARG2 facilitates interaction with demethylated AKAP12 gene promoter and suppresses proliferation in prostate cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Feng Li ◽  
Tingting Lu ◽  
Dongmei Liu ◽  
Chong Zhang ◽  
Yonghui Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Gene Promoter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cycle Arrest

AbstractProstate cancer (PCA) is one of the most common male genitourinary tumors. However, the molecular mechanisms involved in the occurrence and progression of PCA have not been fully clarified. The present study aimed to investigate the biological function and molecular mechanism of the nuclear receptor peroxisome proliferator-activated receptor gamma 2 (PPARG2) in PCA. Our results revealed that PPARG2 was downregulated in PCA, and overexpression of PPARG2 inhibited cell migration, colony formation, invasion and induced cell cycle arrest of PCA cells in vitro. In addition, PPARG2 overexpression modulated the activation of the Akt signaling pathway, as well as inhibited tumor growth in vivo. Moreover, mechanistic analysis revealed that PPARG2 overexpression induced increased expression level of miR-200b-3p, which targeted 3′ UTR of the downstream targets DNMT3A/3B, and facilitated interaction with demethylated AKAP12 gene promoter and suppressed cell proliferation in PCA. Our findings provided the first evidence for a novel PPARG2-AKAP12 axis mediated epigenetic regulatory network. The study identified a molecular mechanism involving an epigenetic modification that could be possibly targeted as an antitumoral strategy against prostate cancer.

scholarly journals Alteration of the Methylation Status of Tumor-Promoting Genes Decreases Prostate Cancer Cell Invasiveness and Tumorigenesis In vitro and In vivo

2006 ◽  
Vol 66 (18) ◽  
pp. 9202-9210 ◽  
Author(s):  
Nicholas Shukeir ◽  
Pouya Pakneshan ◽  
Gaoping Chen ◽  
Moshe Szyf ◽  
Shafaat A. Rabbani
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Methylation Status ◽  
Cell Invasiveness ◽  
Cancer Cell Invasiveness

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

Novel daidzein molecules exhibited anti-prostate cancer activity through nuclear receptor ERβ modulation, in vitro and in vivo studies

2021 ◽  
pp. 1-13
Author(s):  
R. Ranjithkumar ◽  
K. Saravanan ◽  
B. Balaji ◽  
S. Hima ◽  
S. Sreeja ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptor ◽  
In Vivo Studies ◽  
Cancer Activity

scholarly journals YAP1 overexpression contributes to the development of enzalutamide resistance by induction of cancer stemness and lipid metabolism in prostate cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Hsiu-Chi Lee ◽  
Chien-Hui Ou ◽  
Yun-Chen Huang ◽  
Pei-Chi Hou ◽  
Chad J. Creighton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lipid Metabolism ◽  
Critical Issue ◽  
Castration Resistant Prostate Cancer ◽  
Cancer Stemness ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
Transcriptional Complex

AbstractMetastatic castration-resistant prostate cancer (mCRPC) is a malignant and lethal disease caused by relapse after androgen-deprivation (ADT) therapy. Since enzalutamide is innovated and approved by US FDA as a new treatment option for mCRPC patients, drug resistance for enzalutamide is a critical issue during clinical usage. Although several underlying mechanisms causing enzalutamide resistance were previously identified, most of them revealed that drug resistant cells are still highly addicted to androgen and AR functions. Due to the numerous physical functions of AR in men, innovated AR-independent therapy might alleviate enzalutamide resistance and prevent production of adverse side effects. Here, we have identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Functional analyses reveal that YAP1 positively regulates numerous genes related to cancer stemness and lipid metabolism and interacts with COUP-TFII to form a transcriptional complex. More importantly, YAP1 inhibitor attenuates the growth and cancer stemness of EnzaR cells in vitro and in vivo. Finally, YAP1, COUP-TFII, and miR-21 are detected in the extracellular vesicles (EVs) isolated from EnzaR cells and sera of patients. In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.

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