Cell Cycle and Cancer Eukaryotic cell cycle Regulated

Cell Cycle and Cancer

Eukaryotic cell cycle • Regulated by specific cell signaling molecules found in the cytoplasm. • Cell cycle control system – Cell cycle is regulated at certain checkpoints by both internal and external signals – Checkpoint – control point where stop and go ahead signals can regulate the cycle. • Transmitted with the cell by signal transduction pathways

• Signals report whether crucial cellular processes that should have occurred by that point have in fact been completed correctly – Whether or not the cell cycle should proceed • 3 major checkpoints – G 1, G 2 and M phases – G 0 – non dividing state • Cell cycle is regulated at molecular level by a set of regulatory proteins – kinases and cyclins – Growth factors a must for cell division

Cyclin-dependent kinases • Controls the cell cycle, regulates the passage of cells through checkpoints – G 1 – S, and G 2 – M • Kinase – enzyme that removes a phosphate group from ATP and adds it to a protein • Kinases are activated when combined with cyclin

Cell Cycle Checkpoints

Normal cell characteristics • Density Dependent inhibition – crowding cells stop dividing – Cell surface protein sends a cell division inhibiting signal to both cells, preventing moving on in cell cycle • Anchorage dependence – cells must be attached to substratum to divide

Cancer cells • Do not follow the normal signals that regulate the cell cycle. – Divide excessively, invade other tissues and can kill organisms – Continue to divide when growth factors have been depleted, may make their own – Immortal (He. La), can continue dividing indefinitely as long as they have nutrients

Cancer Terms Neoplasm – new, abnormal growth of cells Benign – not cancerous Malignant - cancerous Cancer – cellular growth disorder that results from the mutation of the genes that regulate the cell cycle • Carcinogenesis – development of cancer • •

Characteristics of Cancer Cells • Cancer cells – Lack differentiation, do not contribute to body – Have abnormal nuclei, enlarged, abnormal # of chromosomes – No apoptosis – Form tumors, no contact inhibition, disorganized and multilayered – Not encapsulated – Undergo metastasis and angiogenesis • Telomeres – a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from deterioration. Cancer cells have longer regions so they can continue to reproduce.

Prognosis (probable outcome) 1. Whether the tumor has invaded surrounding tissue 2. Whethere is lymph node involvement 3. Whethere are metastatic tumors in distant parts of the body

Proto-oncogenes • specify proteins that directly and indirectly promote the cell cycle • Found at the end of a stimulatory pathway • A mutated proto-oncogene = oncogene

Tumor-suppressor genes • At the start of inhibitory pathway • Directly or indirectly inhibit the cell cycle • When mutates, inhibitory proteins fail to be active and cell cycle is unchecked. • Ex. P 53, mutated mostly in human cancers, works to turn on the expression of other genes who inhibit cell cycle and stimulates apoptosis.

oncogenes • Cancer causing genes • Cause acceleration of the cell cycle by coding for a faulty receptor protein or specify an abnormal protein product that stimulates the cell cycle to begin. • Can bring about excess cyclin and excess inhibitors of p 53 so that apoptosis does not occur. • Ex. ras. K, ras. N, BRCA 1