Cancer Biology (CH 24) Flashcards
proto-oncogene
produce proteins with normal cellular function; promote cell growth/apoptosis (i.e. Ras); Gain of function mutations cause to become oncogenes
tumor supressor gene
produce proteins involved in negatively regulating cell growth/cell cycle progression (i.e. STATs & JAKs); loss of function mutations allow unregulated cell proliferation.
proteins encoded by tumor supressor genes
intracellular proteins - regulate cell cycle progression; receptors/transducers that inhibit cell proliferation; checkpoint-control proteins; apoptosis promoting proteins;
DNA repair proteins
hallmarks of cancer
self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, limitless replicative potential, tissue invasion and metastasis, sustained angiogenesis
benign tumor
remain clustered (encapsulated) & can be removed
malignant (metastatic) tumor
invade surrounding & distant tissue
angiogenesis
the ability of a tumor to develop new blood vessels. needed for tumor >2mm to grow
promotion of angiogenesis
Tumors secrete factors to induce angiogenesis: VEGF (vascular endothelial growth factor), FGF, TGFa. Tumors also induce surrounding cells to secrete these factors. Degradations of basal lamina of capillaries. Migration of endothelial cells toward tumor.
Endothelial cell proliferation.
Formation of new basement membrane and new elongated capillary.
properties of transformed cells
these cells are immortalized (unlimited number of population doublings) and
display transformed phenotype:
morphology change, grow unattached to ECM, reduced requirement for growth factors, secrete plasminogen activator (degrade ECM), and loss of actin microfilaments
“multi-hit” model
explains that the incidence of cancer increases with age because with an increase in the number of oncogenic mutations, there is an increased likelihood of tumor development & malignancy.
proto-oncogene -> oncogene
Point mutation: constitutively active protein.
Chromosomal translocation: create fusion protein OR alter gene expression (turn on many copies of normal gene).
Gene amplification: multiple copies of growth promoting gene.
Rous Sarcoma Virus (RSV)
first virus identified to cause cancer; retrovirus
acutely transforming retrovirus
contain oncogenes; rapidly induce cancer
slowly transforming retrovirus
lack oncogene; induce cancer by turning on expression of gene where they integrate - may be transforming over a long latency (i.e. Human T Cell Leukemia Virus)