Human Biology BIOL 104 Talk Thirteen Cancer Cell

Human Biology (BIOL 104) Talk Thirteen: Cancer Cell Reproduction (Chapter 10) Gene Regulation (Chapter 16)

What Is Cancer? • Cancer is a disease of altered gene expression that can occur at every level of control, including at the levels of DNA replication, histone acetylation, and activation of transcription factors • Cancer is not a single disease: • In cancer cells, mutations modify cell-cycle control and cells don’t stop growing as they normally would. • Mutations can also alter the growth rate or the progression of the cell through the cell cycle. • For cells to move through each phase of the cell cycle, the cell must pass through checkpoints. • This ensures that the cell has properly completed the step and has not encountered any mutation that will alter its function.

Control of the cell cycle • It is essential that the daughter cells produced be exact duplicates of the parent cell. • Mistakes in the duplication or distribution of chromosomes lead to mutations that may be passed on. • Prevented by internal control mechanisms that operate at three main cell cycle checkpoints. • A point in the eukaryotic cell cycle at which The progression of a cell to the next stage in the cycle can be halted until conditions are favorable. • Occur near the end of G 1, at the G 2/M transition, and during metaphase Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Control of the cell cycle The G 1 Checkpoint: • Point at which the cell commits to the cell division process. • Growth factors play a large role in carrying the cell past the G 1 checkpoint. • In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G 1 checkpoint. • A cell that does not meet all the requirements will not be allowed to progress into the S phase. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Control of the cell cycle The G 2 Checkpoint: • Bars entry into the mitotic phase if certain conditions are not met. • Most important role of the G 2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. • If the checkpoint detects problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Control of the cell cycle The M Checkpoint: • Occurs near the end of the metaphase stage. • Also known as the spindle checkpoint, because it determines whether all the sister chromatids are correctly attached to the spindle microtubules. • The separation of the sister chromatids during anaphase is an irreversible step. • Cycle will not proceed until each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Control of the cell cycle Protein control: • Many proteins, including cyclin B, control these checkpoints. The phosphorylation of cyclin B, a post-translational event, alters its function. • As a result, cells can progress through the cell cycle unimpeded, • even if mutations exist in the cell and its growth should be terminated. • This post-translational change of cyclin B prevents it from controlling the cell cycle and contributes to the development of cancer. Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Negative Regulation of the Cell Cycle Retinoblastoma proteins: • A group of tumor-suppressor proteins common in many cells. • Act primarily at the G 1 checkpoint. • p 53 is a multi-functional protein that has a major impact on the commitment of a cell to division • Acts when there is damaged DNA in cells that are undergoing G 1. • If damaged DNA is detected, p 53 halts the cell cycle and recruits enzymes to repair the DNA. • If the DNA cannot be repaired, p 53 can trigger apoptosis • Mutated p 53 induces cancer formation Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Cancer and the Cell Cycle Proto-oncogenes The genes that code for the positive cell cycle regulators Proto-oncogenes are normal genes that, when mutated in certain ways, become oncogenes, genes that cause a cell to become cancerous. Oncogenes differ from proto-oncogenes in three basic ways 1 - Timing and quality of expression 2 - Structure of protein products 3 – Degree to which their protein products are regulated by cellular signals

DNA mutations • DNA replication is a highly accurate process, but mistakes can occasionally occur • Uncorrected mistakes may sometimes lead to cancer. . • Proofreading failure: The polymerase is unable to determine if the newly added base has paired correctly with the base in the template strand. • Mismatch mutation: The incorrectly added base goes undetected after replication. • Mismatch repair proteins do not remove it from the newly synthesized strand • The altered reading frame codon brings in a different amino acid. • The alternate resulting protein could induce cancer Copyright: Open. Stax Biology for AP Courses, Open. Stax, and Rice University

DNA mutations • In rare cases, mistakes are not corrected, leading to mutations and the induction of cancer. • A point mutation in the RNA template can result in the coding for a alternate amino acid in the growing peptide chain during translation – if the new codon is for a different amino acid • An unwanted STOP command would change or stop protein function which could induce cancer formation • Insertions or deletions resulting in a major frameshift of the reading frame can drastically alter protein translation and induce cancer. Copyright: Edited with permission from Open. Stax Biology for AP Courses, Open. Stax, and Rice University

Six Hallmarks of Cancer 1. Self-sufficiency in growth signals or response 2. Insensitivity to grown inhibitor signals (antigrowth signals) 3. Evasion of programmed cell death (apoptosis) 4. Limitless replicative potential (no senescence) 5. Sustained angiogenesis (stimulation of blood vessel growth) 6. Tissue invasion and metastasis

Progression of cancer • A tumor is said to be benign if it is contained in one location and has not broken through the basement membrane to which normal cells are attached • Benign tumors often cause no health problems to an individual • Can grow big enough to interrupt the functioning of normal tissue • Removal is generally successful as they are not intermingled with other tissue

The Characteristics of Cancer • A cancer cell’s structure is abnormal. • Cancer is a result of a series of mutations in the cell’s genes – – Larger cell nucleus and less cytoplasm Loss of structural specialization Cytoskeleton shrinks Plasma membrane proteins could be lost or altered – New plasma membrane proteins may appear – Changes passed on to cell’s descendants

• Progression of cancer Figure 12. 17 (1) Malignant tumors invade normal tissue • Do not just push healthily cells out of the way • Tumor cells produce protein-degrading enzymes that breaks down the connective tissue that holds cells together • As Malignant tumors invade normal produce that allow them to invade other tissue, they spread to other locations • Metastasis – one or more transformed cells spread to the rest of the body via the blood system

The Characteristics of Cancer • A Cancer cells break away from their home tissue. • B The metastasizing cells become attached to the wall of a blood vessel or lymph vessel. They secrete enzymes that break down part of the wall. Then they enter the vessel. • C Cancer cells creep or tumble along inside blood vessels, then leave the bloodstream the same way they got in. They start new tumors in new tissues. From Wikimedia Commons, a freely licensed media file repository

Cancer Prevention and Survival • Cancer prevention includes changes in lifestyle – Not smoking – Avoiding exposure to the sun – Eating a high-fiber, low-fat diet – Visiting the doctor regularly – Performing regular self-examinations - Chemoprevention

Recommended cancer screening tests

The end! Any questions?