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9-3: When Things Go Wrong…
External Factors that Influence Cell Division:
Chemical Factors

If there are not enough nutrients in the environment, the cell will not divide

If the necessary growth factors are not present, the cell will not divide
Physical Factors

Density-Dependent Inhibition = crowding that prevents cell division
o Cells stop dividing when they form a single layer on the surface of a
medium
o If some cells are removed, those bordering the space divide again until the
space is refilled

Anchorage Dependence = to divide, cells must adhere to a substratum
CANCER
Cancer Cells are abnormal and do NOT exhibit density-dependent inhibition nor
anchorage dependence

Cancer cells divide excessively, invade other tissues and can kill the whole
organism

Cancer cells:
o Are normal cells that have mutated or “transformed” to escape the normal
cell cycle
o Result from accumulating damage in DNA
o Have lost control of their cell cycle

May make growth factors themselves

May have an abnormal growth factor signaling system
o Do not differentiate and do not contribute to the function of a tissue
o Are immortal in that they continue to divide indefinitely, as long as
nutrients are available

(Normal mammalian cells will only divide 100 times in culture
before they stop.)
o Have abnormal nuclei  larger than usual and may contain an abnormal #
of chromosomes
o Are normally recognized by the immune system normally and destroyed
o Do not undergo apoptosis
o Do NOT exhibit density-dependent inhibition or anchorage dependence

If an abnormal cell evades destruction, it may form a tumor
o If it remains at the original site, the mass is called a benign tumor
o If it begins to invade neighboring tissues enough to impair their normal
function, it is called a malignant tumor

May need to develop its own blood supply to support its rapid
growth = angiogenesis

At this point an individual is said to have cancer

Malignant tumors have lost attachments to neighboring cells and
their ECM (extracellular matrix) is altered
o Metastasis = cancer cells break free from the original tumor and spread to
other tissues

Requires radiation and chemotherapy
Origin of Cancer
Normal cell growth requires a careful balance between signals that promote and inhibit
cell division.
Proto-oncogenes = genes that code for proteins which promote the cell cycle and prevent
apoptosis (That is, they speed the cycle up.)

Are normal genes for the cell cycle

Usually are at the end of a stimulatory pathway, which extends from the plasma
membrane to the nucleus
o May be stimulated by injury or other factors

If mutated, they may become oncogenes = cancer-causing genes
o May mistakenly:

Stay “on”, keeping the cell dividing despite external signals

Produce abnormal proteins that stimulate cell division

So far, 100 have been identified in humans.

Ex. BRCA-1 gene  breast and ovarian cancer
predisposition
Tumor-Suppressor Genes = code for proteins that inhibit the cell cycle and promote
apoptosis (That is, they tend to stop the cell cycle)

Produce proteins that recognize when DNA is faulty and initiate apoptosis

p53 and RB genes are among these

When mutated, they no longer give a “stop” signal, and the cell continues to
divide
Other Causes of Cancer:

Damage to DNA repair genes

Damage to telomerase = enzyme that keeps ends of chromosomes (telomeres)
from shortening
o When telomeres shorten to a certain point, the cell stops dividing
o Non-shortening telomeres can divide indefinitely

Some viruses can transform normal cells into cancerous state.

Ex. Retroviruses, papovaviruses (ex. HPV) adenoviruses and herpeviruses
o Transform cells by inserting genome into host cell DNA
o Is permanent, never excises
o Indications are that tumor viruses are effective only in combination
with other events such as exposure to carcinogens.

Carcinogens = cancer-causing agents
o Ex. Chemicals, UV rays, X-rays, radon, asbestos,…