Cell Cycle and Cancer

1. Cell Cycle and Cancer

2. 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

3. 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 • G1, G2 and M phases • G0– 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

4. Cyclin-dependent kinases • Controls the cell cycle, regulates the passage of cells through checkpoints • G1 – S, and G2 – M • Kinase – enzyme that removes a phosphate group from ATP and adds it to a protein • Kinases are activated when combined with cyclin

5. Cell Cycle Checkpoints

6. 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

7. 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 (HeLa), can continue dividing indefinitely as long as they have nutrients

8. 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

9. 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.

11. Prognosis (probable outcome) • Whether the tumor has invaded surrounding tissue • Whether there is lymph node involvement • Whether there are metastatic tumors in distant parts of the body

12. 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

13. 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. P53, mutated mostly in human cancers, works to turn on the expression of other genes who inhibit cell cycle and stimulates apoptosis.

14. 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 p53 so that apoptosis does not occur. • Ex. rasK, rasN, BRCA1