Chromosome compartmentalization alterations in prostate cancer cell lines model disease progression

2021 ◽  
Vol 221 (2) ◽  
Author(s):  
Rebeca San Martin ◽  
Priyojit Das ◽  
Renata Dos Reis Marques ◽  
Yang Xu ◽  
Justin M. Roberts ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Genome Structure ◽  
3D Structure ◽  
Gene Clusters ◽  
Chromosome 21 ◽  
Prostate Cancer Progression ◽  
Cancer Aggressiveness

Prostate cancer aggressiveness and metastatic potential are influenced by gene expression and genomic aberrations, features that can be influenced by the 3D structure of chromosomes inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, from normal epithelium to bone metastasis. We describe spatial compartment identity (A-open versus B-closed) changes with progression in these cell lines and their relation to gene expression changes in both cell lines and patient samples. In particular, 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A, and CDK14. These switches are accompanied by changes in the structure, size, and boundaries of topologically associating domains (TADs). Further, compartment changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation. These results suggest that discrete 3D genome structure changes play a deleterious role in prostate cancer progression. 

scholarly journals Alterations in chromosome spatial compartmentalization classify prostate cancer progression

2021 ◽  
Author(s):  
Rebeca San Martin ◽  
Priyojit Das ◽  
Renata Dos Reis Marques ◽  
Yang Xu ◽  
Rachel Patton McCord
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
3D Structure ◽  
Gene Clusters ◽  
Metastatic Potential ◽  
Chromosome 21 ◽  
Prostate Cancer Progression ◽  
Normal Epithelium ◽  
Chromosome Conformation ◽  
Cancer Aggressiveness

Prostate cancer aggressiveness and metastatic potential are influenced by gene expression, genomic aberrations, and cellular morphology. These processes are in turn dependent in part on the 3D structure of chromosomes, packaged inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, ranging from normal epithelium to bone metastasis. Here, we describe how chromatin compartmentalization identity (A- open vs. B-closed) changes with progression: specifically, we find that 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A, and CDK14. These switches could prelude transcription activation and are accompanied by changes in the structure, size, and boundaries of the topologically associating domains (TADs). Further, compartmentalization changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation: one of the main drivers of prostate cancer.  These results suggest that discrete, 3D genome structure changes play a deleterious role in prostate cancer progression. 

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 Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model

BMC Urology ◽  
2005 ◽  
Vol 5 (1) ◽  
Author(s):  
Christy A Rothermund ◽  
Velliyur K Gopalakrishnan ◽  
James D Eudy ◽  
Jamboor K Vishwanatha
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Related Gene ◽  
Progression Model

scholarly journals Linking obesogenic dysregulation to prostate cancer progression

2015 ◽  
Vol 4 (4) ◽  
pp. R68-R80 ◽  
Author(s):  
Renea A Taylor ◽  
Jennifer Lo ◽  
Natasha Ascui ◽  
Matthew J Watt
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Prostate Gland ◽  
The Body ◽  
Endocrine Function ◽  
Low Grade ◽  
Prostate Cancer Progression ◽  
Cancer Aggressiveness ◽  
Increased Risk

The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies.

Use of a tissue biomarker panel to predict which men with a rising PSA post-definitive prostate cancer therapy will have systemic progression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5017-5017
Author(s):  
R. B. Jenkins ◽  
T. Nakagawa ◽  
T. Kollmeyer ◽  
B. Morlan ◽  
E. Bergstrahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Expression Pattern ◽  
Cancer Progression ◽  
Gene Expression Pattern ◽  
Prostate Cancer Progression ◽  
Definitive Therapy ◽  
Psa Recurrence ◽  
Additional Therapy

5017 Background: The majority of men with prostate cancer are diagnosed with cancers with low mortality. Such men are treated with radical prostatectomy, external beam radiotherapy, or brachytherapy and followed by serum PSA evaluations. Some men with a rising PSA therapy will have local recurrence or metastasis, but many will have no other evidence of recurrent disease other than a rising PSA. The PSA doubling time has been used to determine which of these men deserve adjuvant hormonal ablation, radiation therapy, or observation. We hypothesize that additional biomarkers will predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Methods: We designed a custom array containing 526 RNA targets whose expression has been reported to be altered in association with prostate cancer progression. We included targets from Mayo Clinic prostate cancer research. Together with a second commercial array, 530 genes implicated in prostate cancer progression and 420 other cancer-related genes were evaluated. A case-control design was used to test the association of the expression results with outcome. Cases were men post-radical prostatectomy who developed systemic progression within 5 years after PSA recurrence (N=213). Controls were matched men post-radical prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years (N=213). Results: Of 426 eligible patients, paraffin blocks were available on 418 (98.1%). RNA was prepared from all 418 blocks, and both arrays were both successful on 405 (96.9%) RNAs. Upon univariate analysis, 40 genes were highly significantly over- or under-expressed in the cases versus controls (1x10-22 < p < 1x10-7). Recursive partitioning (RP) selected 4 genes (TPX2, FAM13C1, TOPO2A and TSP2) that distinguished cases from controls. Random Forest analysis selected 24 genes (including 3 of the RP 4). A multivariable ROC analysis using these 24 genes generated an AUC of 0.80 (95% CI: 0.75–0.84). Conclusions: A specific gene expression pattern was significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. No significant financial relationships to disclose.

SELDI protein profiling of dunning R-3327 derived cell lines: Identification of molecular markers of prostate cancer progression

The Prostate ◽  
2007 ◽  
Vol 67 (14) ◽  
pp. 1565-1575 ◽  
Author(s):  
Gunjan Malik ◽  
Elizabeth Rojahn ◽  
Michael D. Ward ◽  
Mathew B. Gretzer ◽  
Alan W. Partin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Markers ◽  
Cell Lines ◽  
Cancer Progression ◽  
Protein Profiling ◽  
Prostate Cancer Progression
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