Big Brothers Are Watching: the Retinoblastoma Family and Growth Control

  • Peter Stiegler
  • Antonio Giordano
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 20)

Abstract

Multicellular organisms consist of numerous types of cells and each of these cells has characteristic properties in its pattern of gene expression, its degree of multiplication rate, its state of differentiation, and its life span. The cellular programs are guided by both inner- and extracellular signals converging onto various molecular pathways. Dependent on this information, the cell decides whether to respond with proliferation, differentiation, quiescence, or apoptosis in gene-directed processes to maintain homeostasis. Loss of genetic integrity affecting either growth-promoting (proto oncogenes) or growth-inhibiting (tumor suppressor genes) sources could be the initial step in the multistep development of neoplasia. While heterozygous mutations of proto oncogenes can be sufficient for cellular transformation, only homozygous mutations of tumor suppressor genes, such as the retinoblastoma protein pRB, have been reported to cause cancer in mammalian cells to date. The tumor suppressor p53 is an exception, as dominant negative mutants have been shown to elicit cellular transformation (Bishop 1991). The majority of cells in a developed mammalian organism are in a non-proliferative, either differentiated or quiescent state, and the commitment to become a particular specialized cell necessitates its withdrawal from the cell cycle. The retinoblastoma protein family members pRB, p 107, and RB2/p 130 have in the past been shown to play a major role for cells to keep these commitments and prevent cells from improperly reentering or improperly staying in the cell-division cycle. In fact, inactivation of the RB family is an integral event for a large number of diverse growth promoting pathways.

Keywords

Migration Tyrosine Serine Beach Estradiol 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Peter Stiegler
  • Antonio Giordano
    • 1
  1. 1.Department of Pathology, Anatomy and Cell Biology and Sbarro, Institute for Cancer Research and Molecular MedicineThomas Jefferson UniversityPhiladelphiaUSA

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