Induction of senescence-associated growth inhibitors in the tumor-suppressive function of retinoids.

Abstract

Retinoids, physiological regulators of cell growth and differentiation, are used in the treatment or chemoprevention of several malignant diseases. This class of compounds can induce growth arrest or apoptosis in tumor cells. Permanent growth arrest of retinoid-treated cells is often assumed to result from retinoid-induced differentiation. Recent studies in breast carcinoma and neuroblastoma cells demonstrated that retinoids can stop tumor cell growth through the program of senescence rather than differentiation. Retinoid-induced tumor suppression is associated with the induction of multiple intracellular and secreted growth-inhibitory proteins. Most of these proteins were also found to be upregulated in senescent cells. The induction of senescence-associated growth inhibitors appears to be an indirect effect of retinoids. Elucidation of the mechanisms responsible for the induction of growth-inhibitory genes in retinoid-treated cells should help in developing agents that would mimic the antiproliferative effect of retinoids in retinoid-insensitive cancers.

• Authors: Igor B Roninson, Milos Dokmanovic
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 88 Issue 1 Pg. 83-94 (Jan 01 2003) ISSN: 0730-2312 [Print] United States
• PMID: 12461777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents
• Retinoids

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Differentiation
• Cellular Senescence
• Humans
• Neoplasms (drug therapy, pathology)
• Neuroblastoma (drug therapy, pathology)
• Retinoids (pharmacology)
• Time Factors
• Tumor Cells, Cultured
• Up-Regulation