 Since the cell cycle is known, now we must ask what controls it  Noted that healthy cells in contact will not divide ◦ Essentially, this is how our skin heals  But what drives the cycle?  Sequential control?  Experiments have shown that proteins control it

Experiment 1 Experiment 2 S S S G1G1 G1G1 M M M When a cell in the M phase was fused with a cell in G 1, the G 1 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 G 1, the G 1 cell immediately entered the S phase—DNA was synthesized. S cells contained something that induced regulation in G 1 cells.

 Conclusion: the S phase proteins work on G 1 nuclei, M phase works on everything  Biologists determined it was a complex of two proteins called mitotic promoting factor (MPF)  Made of cyclin dependent kinase (CDK) and cyclin  Kinase enzymes turn other proteins on and off by phosphorylating them inactive cycle protein >active-P ATP  ADP

 MPF phosphorylates key proteins, inducing mitosis ◦ And, activates a protein that destroys cyclin ◦ So, it shuts off further division when it has been activated  Similar 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 G 0

G1G1 G 1 checkpoint G1G1 G0G0 If a cell receives a go- ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

 Overall, it appears as though there are many factors, internal and external that control the cell cycle  Ex. Kinetochores not attached to microtubules  Ex. Density dependent inhibition  Ex. 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

 Cancer can be thought of as uncontrolled growth of cells ◦ They may 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. Cancer cells 25 µm

 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 ture=related  Unfortunately, these cells can continue to grow if supplied with nutrients ◦ Normal cells divide before dying

 A hexanucleotide sequence TTAGGG  Holds DNA together  A portion of this is lost every time a cell divides  When it is lost, DNA unwinds, cell death  Cancer cells have telomerase ◦ Continually rebuilds the telomeres ◦ They are “ageless”

Cancer cell Blood vessel Lymph vessel Tumor Glandular tissue Metastatic tumor 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. Cancer

 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) and hair follicles, and sex cells

 Common side effects – hair loss and a 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

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