A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma

Area of Science:

• Oncology
• Molecular Biology
• Cell Death Research

Background:

• Aberrant inhibition of programmed cell death (apoptosis) can promote cancer by enabling mutations and therapy resistance.
• While some apoptosis inhibitors are known (e.g., bcl-2 family, baculovirus IAP), their general role in neoplasia remains unclear.

Purpose of the Study:

• To identify and characterize novel apoptosis inhibitors involved in cancer.
• To investigate the expression patterns of a newly identified inhibitor, survivin, in normal and cancerous tissues.

Main Methods:

• Gene cloning and characterization of a novel human IAP apoptosis inhibitor, survivin.
• Analysis of survivin expression in various human cancer cell lines and tissues (lung, colon, pancreas, prostate, breast, lymphomas).
• Functional studies using recombinant survivin to assess its effect on apoptosis in IL-3-deprived B lymphocyte precursors.

Main Results:

• A new human gene, survivin, encoding a unique IAP apoptosis inhibitor was identified.
• Survivin expression is high in fetal tissues, undetectable in adult differentiated tissues, but prominently expressed in transformed cell lines and common human cancers.
• Survivin is also detected in high-grade non-Hodgkin's lymphomas but not low-grade ones; recombinant survivin inhibits apoptosis.

Conclusions:

• Apoptosis inhibition appears to be a common feature in neoplasia.
• Survivin is a potential therapeutic target for developing novel apoptosis-based cancer and lymphoma treatments.