The Nature of Cancer All cells have the capacity to become cancerous Misusing Normal Tools Using Abnormal/Broken Tools Super Tools Broken Tools Cancers are categorized Categorization of Cancers Categorization of Cancers Sarcoma Carcinoma Other Cancers L M M L L L L Carcinoma Sarcoma Cancers develop gradually normal metaplasia Hyperplasia Metaplasia normal Pre-Cancer malignant normal normal Anaplasia Epithelial Mesenchymal Transition (EMT) normal Metastasis Cancers are monoclonal (or are they????) ? Supporting Evidence for Monoclonal Tumors Barr Bodies • Chromosome tightly packaged with proteins (heterochromatin) • No gene transcription from Barr Body • X chromosomes are homologous, meaning that they carry the same genes, but could carry different ‘versions’ of them (alleles) • X chromosomes carry ~1800 genes • One of the genes on the X chromosome encodes glucose-6-phosphate dehydrogenase (G6PD) • There are 2 different alleles (polymorphisms) in the human genome, one more heat resistant than the other. • 30% of African American women are heterozygous for the G6PD gene (they have 2 different alleles in their genomes) ? Cancer cells make energy differently than normal cells Aerobic Glycolysis = the Warburg Effect Glycolysis serves other functions Cancers don’t affect everyone equally Genes altered in cancer typically: • Have a positive role in cell division • Have a negative role in cell division • Have a role in the maintenance of DNA integrity The Behavior of Isolated (cultured) Cancer Cells Cancer cells are often described as “transformed.” Transformed cells behave differently when cultured than ‘non-transformed’ (normal?) cells. Technically, cells are considered “transformed” if they exhibit any one of the following characteristics, and would be considered “more transformed” with increasing numbers of the following phenotypes: Transformed versus normal cells: ….in monolayer normal normal transformed transformed Transformed versus normal cells: ….in monolayer Cells exhibit loss of contact dependence; grow independent of cell-to-cell contact Transformed versus normal cells: ….in suspension Cells exhibit loss of anchorage dependence; grow independent of adhesion to a matrix. Transformed versus normal cells: ….in vivo Cancers result from alternations in DNA Sometimes “genes”, and other times not…but let’s focus on the genes