* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Prostate cancer stem cells Ongoing Projects 3
Gel electrophoresis of nucleic acids wikipedia , lookup
Comparative genomic hybridization wikipedia , lookup
Transcriptional regulation wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Silencer (genetics) wikipedia , lookup
List of types of proteins wikipedia , lookup
Secreted frizzled-related protein 1 wikipedia , lookup
Community fingerprinting wikipedia , lookup
Molecular evolution wikipedia , lookup
Molecular cloning wikipedia , lookup
Deoxyribozyme wikipedia , lookup
Endogenous retrovirus wikipedia , lookup
Non-coding DNA wikipedia , lookup
Transformation (genetics) wikipedia , lookup
Bisulfite sequencing wikipedia , lookup
Promoter (genetics) wikipedia , lookup
DNA vaccination wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
PROSTATE CANCER STEM CELLS ONGOING PROJECTS ‐ 3 GENOMIC AND EPIGENETIC CHANGES EPIGENETIC CHANGES include structural changes in the chroma-n and chemical modifica-ons of the DNA. This results in heritable changes in gene expression. Epigene-c regula-on is frequently altered in cancer and acts in combina-on with gene-c changes during cancer ini-a-on and progression. Normal Tissue Low density CpG sites Using Pyrosequencing technology, we can study the dysregula-on of DNA methyla-on in prostate cancer stem cells. This will lead to a beHer understanding of the mechanisms that lead to cancer stem cell forma-on and to development of new therapies. CpG island Expressed Gene Cancer Silenced Gene Hypomethyla8on of low density CpG sites: • genomic instability • ac-va-on of oncogenes • loss of imprin-ng PYROSEQUENCER Hypermethyla8on of CpG islands: • downregula-on of tumor suppressor genes Methylated CpG site Unmethylated CpG site The best‐known epigene-c marker is DNA methyla-on, which occurs primarily at CpG dinucleo-des. Its dysregula-on in cancer usually leads to genomic instability, ac-va-on of oncogenes and inhibi-on of tumour suppressor genes. Normal Fusion GENOMIC CHANGES include dele-ons, inser-ons and transloca-ons of DNA as well as fusion of different DNA sequences. This can lead to genes being gained or lost or being under the control of the wrong elements. Increased expression of oncogenes or decreseed expression of tumour suppressor genes can lead to cancer. We use a method called FISH (fluorescent in situ hybridisa-on) to detect these fusions by using fluorescent probes that are specific to par-cular DNA sequences. DNA DAMAGE RESPONSE We wish to measure the response of prostate cancer stem cells to cancer therapies including radia-on and chemotherapy. Ini-al therapies for prostate can be successful at shrinking the tumour. However, in some cases a secondary tumour emerges and this is typically resistant to therapy. We hypothesise that prostate cancer stem cells are resistant to radia-on and chemotherapy and are responsible for secondary tumours. HOW TO MEASURE DNA DAMAGE? DNA damaging agents: ‐ Radia-on ‐ Chemotherapeu-c drugs DNA break Cell detects DNA break using proteins that go to site of break. These proteins either signal repair or if damage is too great, the cell will commit suicide. Protein is visualised by immunofluorescence as dots in the nucleus of the cell indica-ng sites of DNA damage. By coun-ng the cells with these foci we can quan-fy damage. Blue dye shows DNA.