Part II

Tumor Suppressor Genes: prevent uncontrolled cell division What is an oncogene? A gene that causes cancer or uncontrolled cell division. Proto-oncogenes: normal, healthy genes that regulate cell growth, cell division, and the ability of the cell to adhere (“stick”) to other cells. A mutation in a proto-oncogene may cause it to become an oncogene (cancer causing) Tumor Suppressor Genes: prevent uncontrolled cell division A mutation in a tumor suppressor gene leads to a predisposition to cancer. However, it appears to take more than one mutated gene (6-8???) for a normal cell to become a cancer cell...

Tumor Suppressor Example… p53: “The Guardian Angel” Gene Monitors DNA during the G1 phase of the cell cycle If damage is detected- •halts cell division •stimulates repair •allows cell division to continue OR •directs cell suicide

p53 is missing or badly damaged in most cancer cells Cigarette smoke ---> p53 damage (p53 damage found in 70-80% of lung cancer) Hmmm… what if we add the p53 protein to cancer cells? -Stops them from dividing! Damaged DNA is not repaired. If other accumulates, the cell can turn cancerous.

Telomeres Highly repetitive DNA on the ends of chromosomes Protect chromosomes from damage Get shorter with each cell division Healthy cells can only divide approx 50 times (Hayflick Limit) before the telomeres become too short and the cell stops dividing (senescence) and dies (apoptosis)

Kids with progeria have short telomeres http://seattlepi.nwsource.com/dayart/20040916/226progeriaXX_closeup.jpg

Telomerase Cancer Cure An enzyme that protects the telomeres and allows cell division to continue (appears to prevent senescence) Most cells inhibit telomerase production White blood cells divide often and do NOT inhibit telomerase Prevents cancer because cells can divide only a finite number of times Cancer Almost all cases involve a mutation of the telomerase inhibitor Cure Inhibit telomerase

Implications for this line of research… Do cancer cells and kids with progeria hold a secret to increased life span? http://biology.plosjournals.org/archive/1545-7885/3/11/figure/10.1371_journal.pbio.0030395.g002-M.jpg