Cancer Chapter 16

VII. Cancer & gene regulation  A. Somatic cell mutations can =cancer  1. caused by chemical carcinogens  2. high energy radiation  3. ex. translocation  a. chromosome breakage & relocation  1. moved near very active promotor  2. broken gene inactive  4. ex.gene amplification(many copies)  5. ex. gene mutations

 B) Proto-oncogenes = normal genes  1) if mutated become oncogenes  2) code for proteins that stimulate mitosis  3) ras gene example (30% of cancers)  a. codes for a G protein called ras 

G protein review (p 110) (p325)  G proteins use GTP energy  G proteins send signals from receptor proteins to transduction cascade  mutated G protein= too much or too little signal

 4) ras G-protein relays growth hormone signal to cascade of protein kinases.  a) transduction of signal results in production of protein that stimulates cell cycle  b) mutated ras gene is an oncogene  c) mutated ras protein constantly triggers cascade of protein kinases regardless of presence of growth factor  d) protein product stimulates cell division (p 325, fig )

 C. tumor-suppressor genes  1. some code for DNA repair proteins  2. some code for adhesion proteins  3. some code proteins that inhibit cell division  4. example:p53 tumor-suppressor gene  a. 50% of cancers show this mutation  b. p53 codes for transcription factor  that promotes production of  cell cycle inhibiting proteins  (CKI p21)

 c. p53 transcription factor activates several different genes  1. gene p21 makes a protein that  binds cyclin-dependent kinases, stopping cell division  2. microRNAs activated by p53 inhibit cell cycle by binding up mRNA blocking it  3. genes for DNA repair activated  4. activates apoptosis genes if DNA can not be repaired 

D. Multi-step model  1. More than one somatic mutation needed to produce cancer cells  2. Explains increased cancer risk with age

E. Inherited Cancer Risk  1. inheriting one oncogene or mutated tumor suppressor gene  a. won’t automatically cause cancer  b. puts you one step closer  2. BRCA1 and BRCA2 are inherited mutations associated with Breast Cancer  a. second most common cancer in USA  b. tumor suppressing genes  c. DNA tests developed

F. Virus caused Cancers  1. implicated in 15% of cases  2. Human Papillomavirus  HPV vaccine protects against HPV types that most commonly cause anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers.  Every year in the U.S., 27,000 people get cancer caused by HPV

HPV actions  HPV Virus block production of tumor suppressor protein RB  Rb inhibits transcription (copying) of genes needed to move to S phase

G.Cyclin Dependent Kinase Review  CDKs =enzymes. turn on or off processes in cell division  CDKs only active when bound to cyclin proteins  Different cyclins activate different CDKs at each stage of cell division  Tumor suppressor genes may activate genes that block CDK action  Mutated CDK or Cyclin genes can be oncogenes

H. Check points – regulated by CDKs  1) G1 checkpoint – cycle initiation  a)controlled by cell size  b) growth factors  c) environment  2) G2 checkpoint – transition to M  a) DNA replication complete  b) DNA damage/mutations  3) M-spindle checkpoint  a) spindle attachment