Apoptosis (the 1992 Frank Rose Memorial Lecture)

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Apoptosis, a regulated form of cell death, is characterized by distinct structural features and cellular events.
• Gene expression critically regulates apoptosis, involving oncogenes and oncosuppressor genes.

Purpose of the Study:

• To elucidate the regulatory roles of oncogenes and oncosuppressor genes in apoptosis.
• To investigate the bivalent regulatory function of c-myc in cell proliferation versus apoptosis.
• To understand how oncogenes like ras and bcl-2 influence apoptosis and cell population expansion.

Main Methods:

• Analysis of gene expression patterns related to apoptosis and cell cycle regulation.
• Investigating the impact of growth factors and cell cycle-blocking agents on c-myc activity.
• Examining the role of p53 in initiating apoptosis via cell cycle arrest.
• Correlating gene expression modulation with cellular states of proliferation and apoptosis.

Main Results:

• c-myc acts as a bivalent regulator, promoting cell proliferation with growth factors or apoptosis under deprivation.
• Oncogenes such as ras and bcl-2 confer resistance to apoptosis, driving rapid cell population expansion.
• The oncosuppressor gene p53 may induce apoptosis by arresting the cell cycle (G1/S phase) in c-myc-expressing cells.
• Chemotherapy resistance and sensitivity are linked to shifts between population expansion and high-turnover states, modulated by gene expression.

Conclusions:

• Gene expression, particularly involving c-myc, ras, bcl-2, and p53, is central to the regulation of apoptosis.
• The interplay between proliferation and apoptosis, influenced by oncogenes and oncosuppressors, determines cellular fate.
• Understanding these molecular mechanisms provides insights into chemotherapy response and resistance.