Development of resistance mechanisms to the growth-inhibitory effects of transforming growth factor-beta during tumor progression.
Members of the transforming growth factor-beta family, especially transforming growth factor-beta type 1, are among the most potent growth-inhibitory factors for epithelial, lymphohematopoietic, and neuroectodermal cells. Resistance to transforming growth factor-beta-mediated growth inhibition is frequently observed in cancers derived from these cell types. We review two important aspects of cancer cell resistance to transforming growth factor-beta: 1) It occurs progressively during the multistep process of tumor progression, and 2) it may encompass a potentially wide range of mechanisms involving transforming growth factor-beta-receptor alterations and cell-signaling defects. Stepwise increases in resistance to the growth-inhibitory action of transforming growth factor-beta may therefore sometimes be attributed to not one but several defects that are involved in transforming growth factor-beta activation, binding, and signaling. These factors accumulate within expanding tumor subclones during disease progression.
Filmus
J
J
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Kerbel
R S
RS
D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D016212:Transforming Growth Factor beta