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The Genetic Basis of Cancer. Gene Technology. Tabacco consumption and lung cancer are correlated -> Environmental factors are important factor for onset of cancer Cancer is a genetic disease -> Mutations can cause cancer!!!. Gene Technology. Carcinogenic Substances cause Mutations.
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The Genetic Basis of Cancer Gene Technology Tabacco consumption and lung cancer are correlated -> Environmental factors are important factor for onset of cancer Cancer is a genetic disease -> Mutations can cause cancer!!!
Gene Technology Carcinogenic Substances cause Mutations
Gene Technology Carcinogenic Substances cause Mutations Fungal (Aspergillus) toxin -> causes liver cancer
Gene Technology Carcinogenic Substances cause Mutations
Skin cancer Gene Technology Cancer cells show characteristics of rapid growing cells: ->high nucleus-to-cytoplasm ratio -> high frequency of mitotic cells -> little specialized structure
Correlation between age and outbreak of cancer Gene Technology
Cancer arises from a single cell -> undergoes one or more mutations in particular genes (responsible for cell growth or control of cell growth) -> these changes in cells cause cancer (funtamental cellular properties are altered) All of them are altered -> most destructive tumor -> cancer Only a few changes -> less dangerous tumor Gene Technology Formation of blood vessels No cell death Cells become immortal No aging of cells
Normal cells and cells transformed by an oncogene Gene Technology
Cell birth – cell death – cell growth Stem cells Gene Technology More differenciated cells
Cell growth – Cell differentiation Gene Technology
Cancer induced in dividing cells Cancer inducing mutations occuring in nondividing cells (neurons or muscle) -> normally no cancer induced -> if cancer in skin or leukemia or cancer in the intestine (differentiated cells) -> cells that initiate tumor are not the differentiated cells but the precusor cells (progenitor cells) -> fully differentiated cells normally do not divide -> no replication -> if they have a mutation -> no big effect -> apoptosis initiated Gene Technology
Cancer cells are used for making cell lines Gene Technology -> to produce recombinant protein in mammalien cell cultures -> cancer cell lines -> immortal cells -> to study gene function in cells
Metastasis: Breaking off of cells from primary tumor -> traveling in blood stream -> leaving blood stream at other places -> formation of secundary tumors (metastasis) Gene Technology ECM -> extracellulare matrix EGM -> epidermal growth factor
Cell growth – Reproduction in Eukaryotic cells Eukaryotes have 2 types of cells: -> diploid cells (2n) -> Most of the cells (in mammalians: somatic cells) -> haploid cells (n) -> just the gametes (in mammalians: egg + sperm) Haploid cells (n) are just used for fertilization -> sexual reproduction -> Meiosis Diploid cells (2n) -> somatic cells -> asexual reproduction -> Mitosis Gene Technology Diploid cells -> 2 sets of chromosomes (2n) -> 2 sets of the genes Haploid cells -> 1 set of chromosomes (n) -> 1 set of genes
Cell growth – Reproduction in Eukaryotic cells 1 diploid cell (2n) Asexual Reproduction in Eukaryotes-> Mitosis -> Replication +Separation of Chromosomes Gene Technology 2 diploid cells (2n)
1 diploid cell (2n) 4 haploid cells (n) Cell growth – Reproduction in Eukaryotic cells SexualReproduction in Eukaryotes-> Meiosis -> Replication + 2x Separation of Chromosomes -> cells are ready for fertilization Gene Technology
Cell growth – Reproduction in Eukaryotic cells Gene Technology
Cell growth – Stages of the cell cycle (Mitosis) Gene Technology
Regulation of cell growth – Stages of the cell cycle (Mitosis) Gene Technology CDKs -> cyclin dependent kinases
Overview of checkpoint controls in the cell cycle (Mitosis) Gene Technology Recognition of Mutations trigger blocking of cell cycle
Cell Death - Apoptosis Gene Technology Apoptosis induced by several protein factors -> p53 one of the proteins that play an important role Loss of p53 makes cells resistant to apoptosis -> length of telomere end determine aging of cells
Telomere Ends determine age of cell Gene Technology
The role of Protein p53 Gene Technology
Proteins participating in controlling cell growth and cell death Gene Technology If mutations in these proteins -> cause cancer Viruses (mainly retroviruses – integrative viruses) can also cause cancer 2 type of proteins are (when mutated) responsible for onset of cancer: -> Proto-Oncogenes -> Tumor repressor genes
Proteins participating in controlling cell growth and cell death Gene Technology
Development of Cancer Gene Technology More than one cancer gene activation necessary to develop cancer
Some tumors are activated by chromosomal rearrangements -> Recombination expresses a oncogene (myc is an oncogene -> transforms cells into cancer cells ) -> recombination makes fusion out of bcr gene and abl (bcr-abl oncogene -> modified protein kinase) -> active oncogene causes leukemia Gene Technology
Some tumors are activated by chromosomal rearrangements -> recombination makes fusion out of bcr gene and abl (bcr-abl oncogene -> modified protein kinase) -> active oncogene causes leukemia Gene Technology Tumor developes
Some drugs (chemotherapy) used for inhibiting kinases -> also bcr-abl Gene Technology Bcr-abl with gleevec
Ras oncogene causes bladder carcinoma Gene Technology Ras activates cell division -> normally switched on and off by GTP/GDP -> Mutation can not be switched off any more -> oncogene
Combination of Ras oncogene and myc oncogene causes exellerates cancer devepment Gene Technology
Cancer can be inherited Gene Technology Retinoblastoma -> eye cancer -> also possible for breast cancer (people with inherited mutation in brca gene in one allele -> will eventially have outbreak of breast cancer)
Gene Technology Cloning of a human bladder tumor oncogene
Tumor cells require blood vessels Tumor cells produce protein factors that stimulate angiogenesis -> formation of blood vessels -> blocking angiogenesis -> reduction in tumor size Gene Technology
Proteins involved in cell growth that are affected by cancer causing mutations Gene Technology
Studying Cancer by Microarray Systems Gene Technology All known genes of the cell immobilized
Studying Cancer by Microarray Systems -> which genes are affected by particular cancer -> which proteins are up-or down regulated Gene Technology
Gene Technology Studying Cancer by Microarray Systems -> which genes are affected by particular cancer -> which proteins are up-or down regulated -> which cells are affected
Studying Cancer by Microarray Systems Gene Technology Some cancers are caused by rearrangements in genome -> recombination between different chromosomes or genes -> determine copy number of affected genes
Challenges for Cancer detection and treatment Detection: -> now: need to have already a tumor (many cells) -> in the future: detection of single cells would be good -> nanoparticles? (could lead to treatment of stimulation of immune system) Treatment: -> now: chemotherapy effective but also a lot of healthy cells are effected -> development of effective drug delivery systems -> primarily cancer cells affected -> use of magnetic nanoparticles attacking tumor cells -> heating particles up Gene Technology
Nanobiotechnology/Nanomedicine Liposomes as drug delivery: