Researchers are studying keratinocytes
derived from a patient with Gorlin Syndrome. Genetic analysis shows PTCH
loss-of-function mutations. When they measure Hedgehog pathway activity, they
find that Smoothened is constitutively active, leading to elevated
transcription of Hedgehog target genes and increased cell proliferation.

Which statement best explains why
these patients develop basal cell carcinomas?

Question

Researchers are studying keratinocytes
derived from a patient with Gorlin Syndrome. Genetic analysis shows PTCH
loss-of-function mutations. When they measure Hedgehog pathway activity, they
find that Smoothened is constitutively active, leading to elevated
transcription of Hedgehog target genes and increased cell proliferation.

Which statement best explains why
these patients develop basal cell carcinomas?

Answer

PTCH mutations cause
aberrant activation of p53-dependent apoptosis, paradoxically promoting
tumorigenesis through up-regulation of basal cell proliferation

Answer

Loss of PTCH reduces
Hedgehog signalling, causing basal cells to proliferate uncontrollably

Answer

PTCH loss-of-function
makes cells more sensitive to UV-induced DNA damage, which directly triggers
carcinoma formation through uncontrolled basal cell proliferation

Answer

Loss
of PTCH function removes inhibition of Smoothened, causing persistent Hedgehog
pathway activation and uncontrolled basal cell proliferation

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Researchers are studying keratinocytes derived from a patient with Gorlin Syndr...

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