scholarly journals KCTD11Tumor Suppressor Gene Expression Is Reduced in Prostate Adenocarcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Francesca Zazzeroni ◽  
Daniela Nicosia ◽  
Alessandra Tessitore ◽  
Rita Gallo ◽  
Daniela Verzella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Prostate Cancer Risk ◽  
The United States ◽  
Suppressor Gene ◽  
Prostate Adenocarcinoma ◽  
Negative Regulator ◽  
Human Prostate ◽  
Cancer Pathogenesis ◽  
Hh Signaling

Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified.KCTD11 (REN)is a tumor suppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and in several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling. Here, we demonstrated thatKCTD11LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog pathway. Low levels ofKCTD11mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led to growth arrest. Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic markers.

scholarly journals Mast Cell-Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1237
Author(s):  
Linda K. H. Teng ◽  
Brooke A. Pereira ◽  
Shivakumar Keerthikumar ◽  
Cheng Huang ◽  
Birunthi Niranjan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Suppressor Gene ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Proteomic Profiling ◽  
Putative Tumor Suppressor Gene ◽  
Invasion And Migration ◽  
And Migration

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

scholarly journals CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids

2021 ◽  
Author(s):  
Megan Lo ◽  
Amnon Sharir ◽  
Michael D Paul ◽  
Hayarpi Torosyan ◽  
Christopher Agnew ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Membrane Composition ◽  
Hh Signaling ◽  
Pathway Regulation ◽  
Patched 1 ◽  
Cancer Signal Transduction

The Hedgehog (HH) pathway is critical for development and adult tissue homeostasis. Aberrant HH signaling can cause congenital malformations, such as digit anomalies and holoprosencephaly, and other diseases, including cancer. Signal transduction is initiated by HH ligand binding to the Patched 1 (PTCH1) receptor on primary cilia, thereby releasing inhibition of Smoothened (SMO), a HH pathway activator. Although cholesterol and several oxysterol lipids, which are enriched in the ciliary membrane, play a crucial role in HH activation, the molecular mechanisms governing the regulation of these lipid molecules remain unresolved. Here, we identify Canopy 4 (CNPY4), a Saposin-like protein, as a regulator of the HH pathway that controls membrane sterol lipid levels. Cnpy4—/— embryos exhibit multiple defects consistent with HH signaling perturbations, most notably changes in digit number. Knockdown of Cnpy4 hyperactivates the HH pathway at the level of SMO in vitro, and elevates membrane levels of accessible sterol lipids such as cholesterol, an endogenous ligand involved in SMO activation. Thus, our data demonstrate that CNPY4 is a negative regulator that fine-tunes the initial steps of HH signal transduction, revealing a previously undescribed facet of HH pathway regulation that operates through control of membrane composition.

Characterization of CD133+/CD44+ human prostate cancer stem cells with ATR-FTIR spectroscopy

The Analyst ◽  
2019 ◽  
Vol 144 (6) ◽  
pp. 2138-2149 ◽  
Author(s):  
Günnur Güler ◽  
Ummu Guven ◽  
Gulperi Oktem
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ftir Spectroscopy ◽  
Molecular Mechanisms ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Stem Cells

Molecular mechanisms and features of prostate cancer stem cells, which are crucial for improving target specific therapies, were elucidated with ATR-FTIR spectroscopy.

scholarly journals Vasectomy and Risk of Aggressive Prostate Cancer: A 24-Year Follow-Up Study

2014 ◽  
Vol 32 (27) ◽  
pp. 3033-3038 ◽  
Author(s):  
Mohummad Minhaj Siddiqui ◽  
Kathryn M. Wilson ◽  
Mara M. Epstein ◽  
Jennifer R. Rider ◽  
Neil E. Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
The United States ◽  
Low Grade ◽  
High Grade ◽  
Follow Up Study ◽  
Increased Risk

Purpose Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease. Patients and Methods Among 49,405 US men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders. Results Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment. Conclusion Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely.

scholarly journals 3p21.3 tumor suppressor gene RBM5 inhibits growth of human prostate cancer PC-3 cells through apoptosis

2012 ◽  
Vol 10 (1) ◽  
pp. 247 ◽  
Author(s):  
Lijing Zhao ◽  
Ranwei Li ◽  
Chen Shao ◽  
Ping Li ◽  
Jian Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Human Prostate ◽  
Human Prostate Cancer

The knowledge and practices of urologists in the United States (US) about standardization of PSA assays.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 207-207
Author(s):  
A. Gupta ◽  
S. F. Shariat ◽  
J. A. Eastham ◽  
P. T. Scardino ◽  
A. J. Vickers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Decision Making ◽  
Reference Range ◽  
Prostate Cancer Screening ◽  
Prostate Cancer Risk ◽  
Clinical Decision ◽  
The United States ◽  
Web Based ◽  
The Us ◽  
The Difference

207 Background: PSA assays can be calibrated to either the WHO or the Hybritech standard. Studies of PSA-based prostate cancer screening have used Hybritech-standardized assays and prostate cancer risk calculators are based on these studies. Testing of patient samples with a WHO calibrated assay gives values that are 22% lower than from those with Hybritech-calibrated assays. Up to 60% of the labs in the US use WHO calibrated assays. We evaluated whether US urologists are aware of the different calibrators and the differences in PSA values. Methods: A random sample of 1,742 US urologists were invited by email to participate in a web-based survey of their knowledge and practices regarding PSA assay standardization. No mention was made of assays or calibration in the invitation. 419 responses were received. Results: Many (56%) US urologists thought that different standards may lead to clinically relevant differences in PSA values. Although 62% reported awareness of the two PSA calibrators, 67% did not know the difference between the two. Only 17% correctly reported the difference between the two standards. Nationally almost 60% of the labs use WHO standardized assays, but in this survey only 5% of the urologists thought that the hospital where they practice used a WHO standardized assay. The rest reported either not knowing the standard (46%) or use of the Hybritech standard (49%). The majority of urologists did not look at the reference range (64%) or for the PSA standard (74%) in the lab reports. Only 25% reported considering the PSA-calibration in their clinical decisions about prostate biopsy, but only a third of them correctly knew the difference between the calibrators. Conclusions: Many US urologists are unaware of the difference caused by WHO versus Hybritech based PSA-assay calibration. Although 60% of clinical laboratories use WHO-calibrated assays, only 5% of urologists are aware of this use in their practice, and a majority of urologists could not correctly explain the difference between the different calibrators. A greater awareness is needed amongst US urologists about the different PSA calibrators, the calibrator in use at their practice, and means to account for different calibrators in clinical decision making. [Table: see text]

scholarly journals PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3

2015 ◽  
Vol 112 (27) ◽  
pp. 8403-8408 ◽  
Author(s):  
Ahmad Salameh ◽  
Alessandro K. Lee ◽  
Marina Cardó-Vila ◽  
Diana N. Nunes ◽  
Eleni Efstathiou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rna Editing ◽  
Noncoding Rna ◽  
Regulatory Mechanism ◽  
Suppressor Gene ◽  
Dominant Negative ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Protein Coding ◽  
Double Stranded Rna

Prostate cancer antigen 3 (PCA3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.

scholarly journals Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk

1998 ◽  
Vol 78 (10) ◽  
pp. 1361-1367 ◽  
Author(s):  
JA Agúndez ◽  
C Martínez ◽  
M Olivera ◽  
L Gallardo ◽  
JM Ladero ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Human Prostate ◽  
Metabolizing Enzymes

Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3

1995 ◽  
Vol 13 (3) ◽  
pp. 168-174 ◽  
Author(s):  
Hiroyoshi Suzuki ◽  
Miburu Emi ◽  
Akira Komiya ◽  
Yoshiyuki Fujiwara ◽  
Ryuichi Yatani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Human Prostate ◽  
Human Prostate Cancer
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