1. Benign vs.

Malignant tumors
a. Benign: abnormal proliferation of cells that remains confined to original location
(i.e. a wart); does not spread to distant body sites
b. Malignant: invades surrounding normal tissue and spreads via the circulatory or
lymphatic systems; Metastisize
2. Clonal Origin of cancer – tumors develop from single cells that begin to proliferate
abnormally (seen by X chromosome inactivation)
3. Consequence of the accumulation of multiple abnormalities over many years –
progressive series of alterations indicated by the development later in life
4. At cellular level, cancer develops as a multi-step process involving mutations and
selections
5. Tumor Initiation – result of genetic alteration leading to abnormal proliferation of a
single cell
6. Tumor Progression – additional mutations occur within cells of the tumor population,
conferring selective advantage to cells, leading to dominance through clonal selection –
occurs throughout development so tumor growth speeds up over time (increasing
malignancy)
7. Carcinogens – substances that cause cancer; for example radiation, chemicals, viruses
a. Solar ultraviolet radiation, carcinogenic chemicals,
b. Carcinogenic African mushroom
c. Mutagens
8. Tumor Promoters (i.e. phorbol esters, estrogen) – contribute to cancer development by
stimulating cell proliferation, rather than by inducing mutations
a. Estrogens: Stimulates the proliferation of cells in the uterine endometrium;
extra estrogen increases chance of endometrial cancer; can be counteracted by
progesterone administration
b. Phorbol Esters: promote tumors and found in a variety of plants
9. Properties of cancer cells
a. Loss of contact inhibition – cell-cell contact does not inhibit the growth of
cancer cells, and cells continue proliferating and migrating in disordered, multilayred
patterns
b. Autocrine growth stimulation – cells begin to stimulate their own proliferation
by producing and secreting their own growth factor
c. ↓ dependency on growth factors – start to secrete own growth factors; secrete
growth factors that promote formation of new blood vessels
d. ▲ in cytoskeleton organization – cells become less adhesive than normal cells
i. Loss of adhesion molecules like E-cadherin leads to morphologic and
cytoskeletal alteration – become rounder than normal
ii. Proteases sdigest extracellular matrix components
e. Metabolic changes
2. Oncogene products acting dominantly – specific genes are capable of inducing cell
transformation (from studies of tumor viruses)
a. First defined in Retroviral (RSv)
3. Proto-oncogene – hypothesis that normal cells contain genes that are closely related to
oncogenes;
a. Typically important cell regulatory genes that encode proteins that function in
signal transduction pathways (src, ras, raf) – oncogenes are the
abnormally/mutated version of these
 b. Raf – amino terminal sequences on raf protein are critical to regulation of its
normal protein kinase activity – unregulated activity drives proliferation
c. Ras proto-oncogene mutations that lead to activation of the oncogene are
caused by chemical carcinogens
i. Active Ras is GTP bound; inactive is GDP bound; oncogene has basically
eliminated Ras response to GAP (GTPase-activating protein) so stays in
the activated state
4. C-oncogene
5. V-oncogene (retrviral origina-RNA tumor viruses)
6. Activation of proto-oncogene
a. Mutations
b. Deletions
c. Gen amplification
d. Translocation
2. Over-expression of normal gene products
3. Expression of chimeric gene products
4. Function of oncogene products
a. Growth factors
b. Receptors
c. Membrane
d. Cytoplasmic and nuclear signal-transduction products
i. Tyrosine Kinases (erbB)
ii. Serine-threonine kinases (raf)
iii. GTP binding proteins (ras)
iv. Transcription factors (myc)
2. Tumor suppressor genes
a. Genes that when absent enable uncontrolled cell-division
i. Retinoblastoma (Rb)
ii. P53
b. Genes that influence cell-cell communication
i. APC and DCC (in colon cancer)
b. Genes involved in quality control of the genome/repair of DNA damage
c. DNA tumor viruses inhibit the normal function of tumor supressor genes
d. Suppressor and dominant acting oncogenes interact and determine tumor
progression (colon cancer)
2. Deregulation of programmed cell death (apoptosis) – cells fial to undergo apoptosis and
live longer life spans contributing to tumor development. Made possible by high levels of
telomerase in many case
a. result in cell survival
b. Accumulations of mutation and drug resistance