Regulation of the Cell Cycle

Internal and External Factors There are many potential reasons why a cell would not be ready to divide Kinetochores not attached to microtubules Density dependent inhibition Anchorage dependence, where cells have to be attached to a substratum (solid surface) to divide

Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

Molecular Control Since the cell cycle is known to be controlled both internally and externally, now we must ask what controls it Sequential? Experiments have shown that proteins are responsible

Experiment 1 Experiment 2 S G1 M G1 S S M M When a cell in the M phase The Rao Johnson Experiment Experiment 1 Experiment 2 S G1 M G1 S S M M When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Something in M phase induced interphase cells to divide. When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G1 cells.

Conclusion: the S phase proteins work on G1 nuclei, M phase works on everything Biologists named these proteins “cyclins” These are used in all three portions of interphase Each is referred to as a “checkpoint” Collectively, they are called growth factors The cell has mechanisms that ensure each phase is complete before moving onto the next We have seen this already with the possibility of a cell entering G0

LE 12-15 G0 G1 checkpoint G1 G1 If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

Cancer Cancer can be thought of as uncontrolled growth of cells They can lack the mechanisms, do not respond properly to them, or have an error in the pathways If they stop, it is at a random point

Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells

A mass of cancer cells is known as a tumor If this tumor stays in the original site – benign If it spreads to surrounding tissue - malignant A individual tumor cell can break free from the group and invade other organs It is said to have metastasized Metastasis http://www.youtube.com/watch?v=rrMq8uA_6iA Unfortunately, these cells can continue to grow if supplied with nutrients Normal cells divide 25-50 before dying

Cancer Lymph vessel Tumor Blood vessel Glandular tissue Metastatic Cancer cell A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part of the body.

Treatments The two most common treatments we have are chemotherapy and radiation treatments Chemotherapy By definition, treatment of any condition via chemicals Our focus is on antineoplastic drugs – cancer fighters Act by targeting rapidly dividing cells However, this also includes healthy cells such as bone marrow (blood cells), hair follicles, and sex cells

Common side effects – hair loss and an compromised immune system Essentially theory is the drugs will kill the cancer faster than the patient If not discovered soon enough, treatment would take too long Radiation Therapy Beam of subatomic particles that damages DNA Has to focus on a tumor

Alternatives With more knowledge on mechanisms of cancer, new treatments are being proposed Viruses are being designed to specifically target cancer cells