CDH1
Cadherin-1 precursor (CAM 120/80) (Epithelial cadherin) (E-cadherin) (Uvomorulin) (CD324 antigen) [Contains: E-Cad/CTF1; E-Cad/CTF2; E-Cad/CTF3] [CDHE] [UVO]
Publications[править]
Cdc6 is a key replication licencing factor with a pivotal role in regulating the process of DNA replication, rendering it an important investigatory focus in tumourigenesis. Indeed, Cdc6 overexpression has been found to be a feature in certain tumours and has been associated as an early event in malignancies. With a focus on pancreatic cancer, there are evidence of its convergence in downstream pathways implicated in major genetic alterations found in pancreatic cancer, primarily KRAS. There is also data of its direct influence on protumourigenic processes as a transcriptional regulator, repressing the key tumour suppressor loci CDH1 (E-Cadherin) and influencing epithelial to mesenchymal transition (EMT). Moreover, gene amplification of Cdc6 as well as of E2F (an upstream regulator of Cdc6) have also been found to be a key feature in tumours overexpressing Cdc6, further highlighting this event as a potential driver of tumourigenesis. In this review, we summarise the evidence for the role of Cdc6 overexpression in cancer, specifically that of pancreatic cancer. More importantly, we recapitulate the role of Cdc6 as part of the DNA damage response and on senescence-an important antitumour barrier-in the context of pancreatic cancer. Finally, recent emerging observations suggest that the potential of the subcellular localisation of Cdc6 in inducing senescence. In this regard, we speculate and hypothesise potentially exploitable mechanisms in the context of inducing senescence via a novel pathway involving cytoplasmic retention of Cdc6 and Cyclin E.
Keywords
- Cdc6
- cytoplasmic Cdc6
- pancreatic cancer
- senescence
- subcellular localisation
The National Comprehensive Cancer Network recommends that women who carry gene variants that confer substantial risk for breast cancer consider risk-reduction strategies, that is, enhanced surveillance (breast magnetic resonance imaging and mammography) or prophylactic surgery. Pathogenic variants can be detected in women with a family history of breast or ovarian cancer syndromes by multigene panel testing. To investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy. We estimated effectiveness and lifetime costs from a payer perspective for two strategies in two hypothetical cohorts of women (40-year-old and 50-year-old cohorts) who meet the National Comprehensive Cancer Network-defined family history criteria for multigene testing. The two strategies were the usual test strategy for variants in BRCA1 and BRCA2 and the seven-gene test strategy for variants in BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, and PALB2. Women found to have a pathogenic variant were assumed to undergo either prophylactic surgery or enhanced surveillance. The incremental cost-effectiveness ratio for the seven-gene test strategy compared with the BRCA1/2 test strategy was $42,067 per life-year gained or $69,920 per quality-adjusted life-year gained for the 50-year-old cohort and $23,734 per life-year gained or $48,328 per quality-adjusted life-year gained for the 40-year-old cohort. In probabilistic sensitivity analysis, the seven-gene test strategy cost less than $100,000 per life-year gained in 95.7% of the trials for the 50-year-old cohort. Testing seven breast cancer-associated genes, followed by risk-reduction management, could cost-effectively improve life expectancy for women at risk of hereditary breast cancer.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
- Breast Neoplasms
- Cost-Benefit Analysis
- Decision Support Techniques
- Early Detection of Cancer
- Female
- Gene Expression Profiling
- Genetic Predisposition to Disease
- Genetic Testing
- Health Care Costs
- Heredity
- Humans
- Life Expectancy
- Magnetic Resonance Imaging
- Mammography
- Mastectomy
- Middle Aged
- Models, Economic
- Patient Selection
- Phenotype
- Predictive Value of Tests
- Prognosis
- Quality-Adjusted Life Years
- Risk Assessment
- Risk Factors
- Watchful Waiting
Keywords
- BRCA
- breast cancer
- cost-effectiveness
- multigene panel testing
Spermatogenesis is a complex biological process that requires precise regulation of gene expression in the germ cells and their surrounding somatic cells. Some testis-specific genes are involved in different stages of spermatogenesis; however, the precise mechanisms of stage-specific spermatogenesis are still not elucidated. In this study, we first examined the expression patterns of SYCP3, Tnp2, CDH1, glial cell-line-derived neurotropic factor (GDNF) and GFRA1 mRNAs on post-natal days (PNDs) 2, 4, 6, 8, 10, 12, 15, 20, 25 and 30 in rat testis. SYCP3 mRNA was firstly detected from PND 15, while Tnp2 transcript was only found on PND 30. CDH1 mRNA was highly expressed before PND 6, but decreased dramatically on PND 8, then gradually increased until it started to decrease after 12 dpp. Low GDNF and GFRA1 mRNAs were found before PND 6, but gradually increased to the peak on PND 12, then gradually decreased to low level. According to the expression patterns of CDH1, GDNF and GFRA1, we hypothesized that PNDs 6-10 are critical period in the early spermatogenesis. We, therefore, explored gene expression pattern on PNDs 6, 8 and 10 using cDNA microarray. 700 (PND 8 vs PND 6), 4519 (PND 10 vs PND 8), and 4298 (PND 10 vs PND 6) differentially expressed genes (≥ 2-fold) were identified from the comparisons, which cover thousands of gene ontology categories (GO terms) and hundreds of signalling pathways. High consistency between microarray data and quantative real-time PCR (qRT-PCR) was verified from five genes (LOC686076, Trib3, Cxcl6, LOC682508 and C2cd4d). These data provide more information to understand the precisely regulatory mechanism at the early stage of spermatogenesis.
MeSH Terms
- Aging
- Animals
- Cell Cycle Proteins
- Female
- Gene Expression Profiling
- Glial Cell Line-Derived Neurotrophic Factor
- Glial Cell Line-Derived Neurotrophic Factor Receptors
- Male
- Microarray Analysis
- RNA, Messenger
- Rats
- Rats, Wistar
- Real-Time Polymerase Chain Reaction
- Spermatogenesis
- Testis
Domesticated ungulate pluripotent embryonic stem (ES) cell lines would be useful for generating precise gene-modified animals. To date, many efforts have been made to establish domesticated ungulate pluripotent ES cells from early embryos without success. Here, we report the generation of porcine-induced pluripotent stem (iPS) cells using drug-inducible expression of defined factors. We showed that porcine iPS cells expressed alkaline phosphatase, SSEA3, SSEA4, Tra-1-60, Tra-1-81, Oct3/4, Nanog, Sox2, Rex1 and CDH1. Pig iPS cells expressed high levels of telomerase activity and showed normal karyotypes. These cells could differentiate into cell types of all three germ layers in vitro and in teratomas. Our study reveals properties of porcine pluripotent stem cells that may facilitate the eventual establishment of porcine ES cells. Moreover, the porcine iPS cells produced may be directly useful for the generation of precise gene-modified pigs.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Bone Marrow Cells
- Cell Culture Techniques
- Cell Differentiation
- Cell Line
- Cell Shape
- Cellular Reprogramming
- Cluster Analysis
- Doxycycline
- Embryonic Stem Cells
- Epigenesis, Genetic
- Fibroblasts
- Gene Expression Profiling
- Genetic Vectors
- Germ Layers
- Humans
- Induced Pluripotent Stem Cells
- Lentivirus
- Promoter Regions, Genetic
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Analysis, DNA
- Sus scrofa
- Transduction, Genetic
Longevity related genes were investigated concerning promoter methylation. SIRT3, SMARCA5, HTERT and CDH1 promoters were analyzed in peripheral blood in relation to gender, age and Alzheimer's disease (AD). Methylation Specific PCR assay (MSP) was used. There were no significant differences in methylation frequencies of SIRT3, SMARCA5 and CDH1 among young, elderly and AD groups (p> 0.05), showing no association with aging or AD. On the other hand, HTERT methylation frequency was associated with the aging process, in that AD patients differed from elderly controls (p=0.0086), probably due to telomere and immune dysfunctions involved in AD pathogenesis.
MeSH Terms
- Adenosine Triphosphatases
- Aged
- Aging
- Alzheimer Disease
- Antigens, CD
- Cadherins
- Chromosomal Proteins, Non-Histone
- DNA Methylation
- Humans
- Mitochondrial Proteins
- Polymerase Chain Reaction
- Promoter Regions, Genetic
- Sirtuin 3
- Sirtuins
- Telomerase