scholarly journals Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14

2015 ◽  
Vol 95 (4) ◽  
pp. 386-389 ◽  
Author(s):  
Malte Böhm ◽  
Christiane Maier ◽  
Rainer Küfer ◽  
Albrecht Röpke ◽  
Walther Vogel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Genetic Basis ◽  
Cancer Susceptibility ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Caucasian Men ◽  
Chromosome 13Q14 ◽  
Exon 10

Introduction: Prostate cancer is the most frequent malignancy found to occur in Caucasian men, but its genetic basis remains elusive. A prostate cancer-susceptibility locus has been identified on chromosome 13q14. The tumour suppressor gene deleted in cancer cells 1 (DICE1/INTS6) is located within this interval on 13q14.3. Materials and Methods: We performed mutation analysis of the DICE1/INTS6 gene in thirteen German prostate cancer families. Results and Conclusion: None of the patients harboured DICE1 mutations, and similar frequencies of the previously identified 13 bp deletion polymorphism in the DICE1 promoter were observed in the familial prostate cancer patients as compared with sporadic prostate cancer patients and controls. However, in one family with three affected brothers, the variations c.1215A>C (p.T405T) in exon 10 and c.2568A>G (p.S856S) in exon 17 were detected in a heterozygous pattern. In sporadic prostate cancer patients, variant c.2568A>G (p.S856S) was detected in 10/325 (3.08%) compared with 5/207 (2.42%) control samples (p > 0.05). We conclude that DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.

scholarly journals Association Between XRCC1 ARG399GLN and P53 ARG72PRO Polymorphisms and the Risk of Gastric and Colorectal Cancer in Turkish Population

2011 ◽  
Vol 62 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Ayse Engin ◽  
Bensu Karahalil ◽  
Ali Karakaya ◽  
Atilla Engin
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Excision Repair ◽  
Turkish Population ◽  
Suppressor Gene ◽  
Good Prognosis ◽  
Tumour Suppressor Gene ◽  
Increased Risk

Association Between XRCC1 ARG399GLN and P53 ARG72PRO Polymorphisms and the Risk of Gastric and Colorectal Cancer in Turkish PopulationGastric cancer is one of the most common cancers of the gastrointestinal system, and its overall five-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence.As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.

104 Loss of speckle-type POZ protein (SPOP) during prostate cancer progression indicates its role as tumour suppressor gene

2014 ◽  
Vol 13 (1) ◽  
pp. e104
Author(s):  
Briones J. Rubio ◽  
I. Casanova-Salas ◽  
M. García-Flores ◽  
A. Calatrava ◽  
J. Casanova ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Prostate Cancer Progression

scholarly journals Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1404
Author(s):  
Hye-Jin You ◽  
Byong-Chul You ◽  
Jong-Kwang Kim ◽  
Jae-Min Park ◽  
Bo-Seul Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Castration Resistant Prostate Cancer ◽  
Normal Prostate ◽  
Prostate Cancer Development ◽  
Kinase A

Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC.

scholarly journals Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 239 ◽  
Author(s):  
I Ruma ◽  
Rie Kinoshita ◽  
Nahoko Tomonobu ◽  
Yusuke Inoue ◽  
Eisaku Kondo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Immunoglobulin Superfamily ◽  
Prostate Cancer Progression ◽  
Transmembrane Glycoprotein ◽  
Mtorc1 Signaling ◽  
Ampk Activity ◽  
In Vivo Growth

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.

scholarly journals Prostate cancer progression in Afro-Caribbean men: Should we be using the same active surveillance protocols as Caucasian men?

2020 ◽  
Vol 19 ◽  
pp. e1918
Author(s):  
E. Osinibi ◽  
V. Stavrinides ◽  
F. Giganti ◽  
C.M. Moore
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Caucasian Men

Role played by BRCA1 in regulating the cellular response to stress

2003 ◽  
Vol 31 (1) ◽  
pp. 257-262 ◽  
Author(s):  
P.M. Gilmore ◽  
J.E. Quinn ◽  
P.B. Mullan ◽  
H.N. Andrews ◽  
N. McCabe ◽  
...  
Keyword(s):  
Cellular Response ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Breast Cancer Susceptibility Gene ◽  
Dna Breaks ◽  
Double Strand Dna Breaks ◽  
Response To Stress

BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor gene that is mutated in the germline of women with a genetic predisposition to breast and ovarian cancer. In this review, we examine the role played by BRCA1 in mediating the cellular response to stress. We review the role played by BRCA1 in detecting and signalling the presence of DNA damage, particularly double-strand DNA breaks, and look at the evidence to support a role for BRCA1 in regulating stress response pathways such as the c-Jun N-terminal kinase/stress-activated protein kinase pathway. In addition, we examine the role played by BRCA1 in mediating both cell-cycle arrest and apoptosis following different types of cellular insult, and how this may be modulated by the presence or absence of associated proteins such as p53. Finally, we explore the possibility that many of the functions associated with BRCA1 may be based on transcriptional regulation of key downstream genes that have been implicated in the regulation of these specific cellular pathways.

Abstract 3448: ERG-negative index tumor status combined with obesity predict prostate cancer progression in Caucasian American prostate cancer patients

2016 ◽  
Author(s):  
Jennifer Cullen ◽  
Denise Young ◽  
Yongmei Chen ◽  
Michael S. Degon ◽  
Wagner Baptiste ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Negative Index ◽  
Prostate Cancer Progression ◽  
Caucasian American ◽  
Index Tumor

ErbB1–4 expression in prostate cancer patients and its correlation to patients’ ethnicity and outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14615-14615
Author(s):  
R. Ben-Yosef ◽  
I. Barnea ◽  
D. Sarid ◽  
A. Vexler ◽  
S. Marmor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Free Probability ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Over Expression ◽  
Hormonal Manipulation ◽  
Cancer Specimen ◽  
Worse Prognosis

14615 Background: ErbB family is involved in both cancer progression and treatment response in solid tumors. Few inconclusive studies reported on ErbB over-expression in prostate cancer. We investigated ErbB1–4 expression in prostate cancer patients and its correlation to patients ethnicity and outcome. Methods: ErbB expression was evaluated by immunohistochemistry of prostate cancer specimen using polyclonal antibody (Santa Cruz, CA). The staining was recorded as negative (0/+1), moderately positive (+2) and highly positive (+3). Kattan nomogram was used to predict 5-yr progression-free probability, assuming that all patients received external beam radiation therapy (a total dose of 78 Gy) and hormonal manipulation. Origin was counted in all 43 patients: Ashkenazic patients were defined as those who immigrated from East/West Europe or North America and Sephardic patients - from Middle East and North Africa. Results: ErbB1 (+2/+3) was over-expressed in 12 and 7 patients for a total of 19/43 (44%). ErbB2 over-expression (+2/+3) was not found in all patients. ErbB3 over-expression of +2 was seen in 2 patients and none had +3 (2/43, 5%). ErbB4 over-expression (+2/+3) was seen in 5 and 11 patients for a total of 16/43 (37%). 22 patients were Ashkenazic and 21 - Sephardic. ErbB1 over-expression in Ashkenazic and Sephardic groups was 9/22 (41%) and 10/21 (48%). ErbB4 over-expression in the two groups was 7/22 (32%) and 9/21 (43%). Kattan score of <80 was seen in 20/43 and <60 in 7/43 patients. ErbB1 over-expression was noted in 11/20 and in 4/7 patients. ErbB4 over-expression was seen in 7/20 and in 4/7 patients. In both ErbB1 and ErbB4 over-expression and Kattan nomogram of <80 and <60 the Sephardic ethnicity dominated-7/11 (64%), 3/4 (75%), 5/7 (71%) and 3/4 (75%). Conclusions: ErbB1 and ErbB4 over-expression is presented in 43% and 37% patients while ErbB3 was over-expressed in 5%; no over-expression of ErbB2 was observed. Ashkenazic and Sephardic ethnicity were evenly distributed in the over-expressed ErbB1 and ErbB4 patients. However, a tendency to a worse prognosis, based on Kattan nomogram, was seen in over-expressed ErbB1 and ErbB4 patients from Sephardic ethnicity. Further studies on ethnicity and ErbB prevalence and prognosis are warranted. No significant financial relationships to disclose.

Variation in UDP glucouronyltransferase (UGT) genes associated with prostate cancer mortality.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 44-44
Author(s):  
M. Kohli ◽  
D. W. Mahoney ◽  
H. S. Chai ◽  
D. W. Hillman ◽  
D. R. Rider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Cox Regression ◽  
Prostate Cancer Progression ◽  
Androgen Ablation ◽  
Principle Components Analysis ◽  
Specific Mortality ◽  
Cancer Specific Mortality

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.

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