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S-138 Chapter 12 Biosignaling
Answer
(a) On exposure to heat, TRPV1 channels open, causing an influx of Na� and Ca2� into the
sensory neuron. This depolarizes the neuron, triggering an action potential. When the
action potential reaches the axon terminus, neurotransmitter is released, signaling the
nervous system that heat has been sensed. 
(b) Capsaicin mimics the effects of heat by binding to and opening the TRPV1 channel at
low temperature, leading to the false sensation of heat. The extremely low EC50 indi-
cates that even very small amounts of capsaicin will have dramatic sensory effects. 
(c) At low levels, menthol should open the TRPM8 channel, leading to a sensation of cool; at
high levels, both TRPM8 and TRPV3 will open, leading to a mixed sensation of cool and
heat, such as you may have experienced with very strong peppermints. 
22. Oncogenes, Tumor-Suppressor Genes, and Tumors For each of the following situations, provide a
plausible explanation for how it could lead to unrestricted cell division.
(a) Colon cancer cells often contain mutations in the gene encoding the prostaglandin E2 receptor.
PGE2 is a growth factor required for the division of cells in the gastrointestinal tract.
(b) Kaposi sarcoma, a common tumor in people with untreated AIDS, is caused by a virus carrying a
gene for a protein similar to the chemokine receptors CXCR1 and CXCR2. Chemokines are cell-
specific growth factors.
(c) Adenovirus, a tumor virus, carries a gene for the protein E1A, which binds to the retinoblastoma
protein, pRb. (Hint: See Fig. 12–48.)
(d) An important feature of many oncogenes and tumor suppressor genes is their cell-type speci-
ficity. For example, mutations in the PGE2 receptor are not typically found in lung tumors.
Explain this observation. (Note that PGE2 acts through a GPCR in the plasma membrane.)
Answer
(a) These mutations might lead to permanent activation of the PGE2 receptor. The mutant
cells would behave as though stimulatory levels of PGE2 were always present, leading to
unregulated cell division and tumor formation. 
(b) The viral gene might encode a constitutively active form of the receptor, such that the
cells send a constant signal for cell division. This unrestrained division would lead to
tumor formation. 
(c) E1A protein might bind to pRb and prevent E2F from binding, so E2F is constantly
active as a transcription factor. It constantly activates genes that trigger cell division, so
cells divide uncontrollably. 
(d) Lung cells do not normally respond to PGE2 because they do not express the PGE2
receptor; mutations resulting in a constitutively active PGE2 receptor do not affect lung
cells.
23. Mutations in Tumor Suppressor Genes and Oncogenes Explain why mutations in tumor
suppressor genes are recessive (both copies of the gene must be defective for the regulation of cell
division to be defective), whereas mutations in oncogenes are dominant.
Answer A tumor suppressor gene in its normal cellular form encodes a protein that re-
strains cell division. Mutant forms of the protein fail to suppress cell division, but if either of
the two alleles of the gene present in the individual encodes a normal protein, normal function
will continue. Only if both alleles are defective will the suppression of cell division fail, leading
to unregulated division. An oncogene in its normal form encodes a regulatory protein that sig-
nals the cell to divide, but only when other, external or internal factors (such as growth fac-
tors) signal cell division. If a defective oncogene product is formed by either of the two alleles,
unregulated cell growth and division will occur: the mutant protein sends the signal for cell
division, whether or not growth factors are present. 
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