Cancer A Disease Resulting from Uncontrolled Cell Growth

Due to lack of specialization, cancer cells have a different appearance than surrounding cells. Cancer cells have enlarged nuclei and may have extra chromosomes. They are genetically unstable and accumulate mutations. Normal cervical cells Precancerous cervical cells Cancerous cervical cells Properties of Cancer Cells

Non-cancerous cells form sheets. Cancer cells grow into tumors, showing a lack of contact inhibition. Cancer cells do not respond to signals from Growth factors—stimulate or inhibit cell division Apoptosis factors—promote death of cells with damaged DNA Apoptosis factors—promote death of cells with damaged DNA Properties of Cancer Cells

Cancer cells divide more frequently and for an unlimited number of times due to an abundance of telomerase, an enzyme that repairs the ends of chromosomes Cancer cells show metastasis, an invasion of other tissues Angiogenesis: cancerous tumors grow new blood vessels for delivery of nutrients and oxygen Properties of Cancer Cells

Cancer is the result of multiple mutations causing uncontrolled growth Angiogenesis: Formation of new blood vessels, allows tumor to grow to larger size

Normal Cell Growth Involves the Cell Cycle with Mitosis G1 cytoplasm doubles S chromosomes replicate G2 assembly of components for division cytokinesis P M A T Mitosis Mitosis includes P = prophase M = metaphase M = metaphase A = anaphase T = telophase Interphase includes G1 = growth phase 1 S = synthesis phase S = synthesis phase G2 = growth phase 2 Interphase

Mitosis = Chromosomal Division Leading to Genetically Identical Nuclei Chromosomes align individually at the cell equator so each daughter cell receives one copy of each chromosome

Control of the Cell Cycle Mechanisms for controlling progress through the cell cycle Mechanisms for controlling progress through the cell cycle Extracellular Signals Extracellular Signals Control the timing of cell division Control the timing of cell division Transitions Transitions Orderly progression from one stage of cell cycle to another Orderly progression from one stage of cell cycle to another Depend on the production of proteins called cyclins Depend on the production of proteins called cyclins Checkpoints Checkpoints Delay progression to next stage if cell must repair damage Delay progression to next stage if cell must repair damage

Control of the Cell Cycle Involves Activities at Transitions and Checkpoints G1 S G2 cytoplasm doubles chromosomes replicate assembly of components for division cytokinesis P M A T Mitosis G1  S Transition G2  M Checkpoint DNA Damage Checkpoint ApoptosisCheckpoint G2  M TransitionSpindleAssemblyCheckpoint G1  S Checkpoint S  G2 Transition Signals initiate self-destruction if DNA damage is severe

Cancer-Causing Mutations Occur in Two Types of Genes Proto-oncogene stimulates cell division Oncogene overstimulates cell division mutation Tumor Suppressor Gene inhibits cell division Mutated Tumor Suppressor Gene cannot influence cell cycle mutation

Mutations That Cause Cancer Gene Type Normal Function In Cancer Mutation Type Proto- Oncogene In response to extracellular or intracellular signals, promotes cell division and prevents apoptosis  Oncogene Promotes cell division in absence of signals Dominant Tumor Suppressor Gene Inhibits cell division and promotes apoptosis Active gene product no longer available to control cell division Recessive example Ras examples RB p53

Ras Proto-Oncogene In response to growth factor binding at receptor, the Ras gene product combines with GTP to promote cell division In cancer cells, the RAS gene product is locked into its GTP-binding shape and does not require a signal at the receptor in order to stimulate cell division

In Normal Cells, the Rb Gene Product Controls the G1  S Transition RB = product of Retinoblastoma gene, inhibits action of E2F until chemically modified due to buildup of CDK-cyclins (intracellular signals) In people who are heterozygous for a mutation in the RB gene (Rb + Rb - ), there is a tendency for the functional copy of the RB gene (Rb + ) to mutate to Rb -. Retinal cancer develops because growth of tumor cells is no longer controlled at the the G1  S transition. E2F = transcription factor required to activate genes for DNA synthesis

In Normal Cells, the p53 Gene Product Acts at the G1  S Checkpoint Preventing Entry Into S Phase If DNA Is Damaged p21 inhibits intracellular signals that would activate E2F p53 = transcription factor that causes p21 to be produced Cells with damaged DNA do not pass the G1  S checkpoint In cancer cells the mutated p53 gene product no longer stimulates p21 production. Cells will pass the G1  S checkpoint even when chromosomal damage exists.

In Normal Cells, the p53 Gene Product Stimulates Apoptosis If DNA Damage Cannot Be Repaired p53 gives an internal signal for apoptosis In cancer cells, a mutated p53 gene product no longer initiates self-destruction. Cells with damaged DNA can divide and more DNA damage can be accumulated. p53 is the most frequently mutated of all known cancer-causing genes, contributing to many types of cancer.

Causes of Cancer HeredityHeredity –tendency to develop cancer can be inherited due to mutations in tumor suppressors, such as BRCA1 and RB –Tendency to inherit thyroid cancer is linked to the RET proto-oncogene Environmental CarcinogensEnvironmental Carcinogens –agents that contribute to cancer development, often by causing mutations

Causes of Cancer Environmental CarcinogensEnvironmental Carcinogens –Radiation ultraviolet radiation in sunlightultraviolet radiation in sunlight nuclear radiationnuclear radiation radon gasradon gas –Organic chemicals found in tobacco smoketobacco smoke pollutantspollutants –Viruses hepatitis B and C viruseshepatitis B and C viruses Epstein-Barr virusEpstein-Barr virus human papillomavirushuman papillomavirus HIVHIV

Cancer Prevention Protective BehaviorsProtective Behaviors –Avoid Carcinogens –Get regular screening tests –Get vaccinated Dietary HabitsDietary Habits –Avoid excess weight gain –Exercise regularly –Exclude foods that promote cancer– salt-cured or smoked foods, excess alcohol –Limit foods that are high in saturated fat –Include protective foods with fiber, vitamins A and C, and cruciferous vegetables

Treatment of Cancer Traditional TherapiesTraditional Therapies –Surgery –Radiation –Chemotherapy restore immune function with bone marrow transplantsrestore immune function with bone marrow transplants Newer TherapiesNewer Therapies –Immunotherapy –p53 gene therapy Genetically-engineered adenovirus that can infect and kill p53-deficient cancer cellsGenetically-engineered adenovirus that can infect and kill p53-deficient cancer cells –Antiangiogenic drugs to inhibit blood vessel formation –Targeted therapy acting on specific molecules Herceptin blocks growth factor receptors on breast cancer cellsHerceptin blocks growth factor receptors on breast cancer cells Gleevec inhibits the action of a faulty tyrosine kinase related to uncontrolled bone marrow cell reproduction in Chronic Myelogenous LeukemiaGleevec inhibits the action of a faulty tyrosine kinase related to uncontrolled bone marrow cell reproduction in Chronic Myelogenous Leukemia