Key Concepts of Section 24.4

• Mutations that permit receptors for growth factors to dimerize in the absence of their normal ligands lead to constitutive receptor activity (see Figure 24-20). Overproduction of growth-factor receptors can have the same effect and lead to abnormal cell proliferation.

• Most tumor cells produce constitutively active forms of one or more intracellular signal-transducing proteins, causing growth-promoting signaling in the absence of normal growth factors (see Figure 24-21).

• Inappropriate production of nuclear transcription factors such as FOS, JUN, and MYC can induce transformation. In Burkitt’s lymphoma cells, MYC is translocated close to an antibody gene, leading to overproduction of MYC (see Figure 24-23).

• Many genes that regulate normal developmental processes encode proteins that function in various signaling pathways. Their normal roles in regulating where and when growth occurs are reflected in the character of the tumors that arise when these genes are mutated.

• Loss of signaling by TGF-β, a negative growth regulator, promotes cell proliferation and development of malignancy (see Figure 24-24).

• Overexpression of anti-apoptotic genes or loss of pro-apoptotic genes promotes tumorigenesis. The pro-apoptotic gene p53 is frequently mutated in cancers.