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PMID: 7859736 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of apoptosis by the retinoblastoma gene product.

The EMBO journal ·Vol. 14 ·No. 3 ·1995-02-01 ·Pages 461-72

Haas-Kogan DA, Kogan SC, Levi D, Dazin P, T'Ang A, Fung YK, Israel MA

Abstract

Tissue homeostasis and the prevention of neoplasia require regulatory co-ordination between cellular proliferation and apoptosis. Several cellular proteins, including c-myc and E2F, as well as viral proteins such as E1A, have dual functions as positive regulators of apoptosis and proliferation. The product of the retinoblastoma tumor suppressor gene, pRb, binds these proteins and is known to function in growth suppression. To examine whether pRb may function as a negative regulator of both proliferation and apoptosis, we analyzed apoptosis induced in transfected derivatives of the human osteosarcoma cell line SAOS-2. Ionizing radiation induced apoptosis in a time- and dose-dependent manner in SAOS-2 cells, which lack pRb expression. In both a transient and stable transfection assay, SAOS-2 derivatives expressing wild-type (wt) pRb exhibited increased viability and decreased apoptosis following treatment at a variety of radiation doses. Expression in SAOS-2 of a mutant pRb that fails to complex with several known binding partners of pRb, including E1A and E2F, did not protect SAOS-2 cells from apoptosis. Radiation exposure induced a G2 arrest in SAOS-2 and in derivatives expressing pRb. Inhibition of DNA synthesis and cell cycle progression by aphidicolin treatment failed to protect SAOS-2 cells or pRb-expressing isolates from undergoing apoptosis. Our data document a novel function for pRb in suppressing apoptosis and suggest that several proteins shown to induce apoptosis, including E1A, E2F and c-myc, may do so by interfering with the protective function of pRb.

MeSH Terms
Aphidicolin/pharmacology Apoptosis/physiology,radiation effects Cell Cycle/drug effects,radiation effects Dose-Response Relationship, Radiation Genes, Retinoblastoma/genetics,physiology Humans Osteosarcoma Radiation Tolerance/genetics,physiology Retinoblastoma Protein/genetics,physiology Transfection Tumor Cells, Cultured X-Rays/adverse effects
Chemicals
Retinoblastoma Protein Aphidicolin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Haas-Kogan D A
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0520.
Kogan S C
Levi D
Dazin P
T'Ang A
Fung Y K
Israel M A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-02-01
Pages
461-72
Language
English
Region
England
NLM ID
8208664
PMCID
PMC398104
Subset
IM
Grants
NCI NIH HHS · CA-09215 · United States
External Links
PubMed source PMC Full Text View journal details
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