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Related Experiment Videos

The bcl-2 oncogene and apoptosis.

D M Hockenbery1

  • 1Department of Medicine, Washington University School of Medicine, St Louis, MO 63110.

Seminars in Immunology
|December 1, 1992
PubMed
Summary

The bcl-2 oncogene, activated in follicular lymphoma, inhibits apoptosis. Overexpression of bcl-2 in transgenic mice reveals its role as an intracellular survival factor in B cells and thymic education.

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Area of Science:

  • Molecular biology
  • Cancer research
  • Immunology

Background:

  • The bcl-2 oncogene is frequently activated by the t(14;18) chromosomal translocation in human follicular lymphomas.
  • The bcl-2 protein is known to inhibit apoptosis, a programmed cell death process, across various experimental systems.
  • While associated with the inner mitochondrial membrane, the precise biochemical function of bcl-2 remains elusive.

Purpose of the Study:

  • To investigate the role of the bcl-2 oncogene and its protein product in apoptosis and cellular survival.
  • To explore the in vivo functions of bcl-2, particularly in the context of B cell development and thymic education.
  • To understand the implications of bcl-2 dysregulation in human cancers and its potential interaction with other tumor suppressors like p53.

Main Methods:

  • Analysis of the t(14;18) chromosomal translocation in human follicular lymphoma samples.
  • In vitro and in vivo experiments to assess the anti-apoptotic function of bcl-2.
  • Biochemical studies to determine the function of the bcl-2 protein.
  • Generation and study of transgenic mice overexpressing bcl-2.

Main Results:

  • The bcl-2 oncogene's activation is linked to follicular lymphoma development.
  • Experimental evidence confirms bcl-2's potent inhibition of apoptosis.
  • Transgenic mice studies demonstrate bcl-2's function as an intracellular survival factor in memory B cells and during thymic education.
  • Potential alterations in other apoptosis regulators, like the p53 tumor suppressor gene, are implicated in human tumorigenesis.

Conclusions:

  • The bcl-2 oncogene plays a critical role in preventing apoptosis, contributing to lymphomagenesis.
  • Bcl-2 acts as an intracellular survival factor, influencing immune cell development and homeostasis.
  • Further research into apoptosis regulators like p53 is crucial for understanding cancer development.

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