Wild-type p53-induced apoptosis in a Burkitt lymphoma cell line is inhibited by interferon gamma.
The tumor suppressor p53 plays a central role in negative growth control, including growth arrest and apoptosis. Interferons (IFNs) are capable of modulating a variety of cellular responses, including apoptosis. In this study, we have evaluated the influence of gamma- and alpha-interferon (IFN) on wild-type (wt) p53-induced apoptosis using a Burkitt lymphoma cell line, BL41, transfected with a temperature-sensitive p53 construct, gamma-IFN, but not alpha-IFN, was found to protect cells from wt p53-induced apoptosis. The gamma-IFN-dependent protection was due neither to down-regulation of p53, nor to the p53-induced genes, p21 (WAF-1) and bax, nor to up-regulation of bcl-2 or bcl-xL. Expression of the proto-oncogene c-myc, implicated in the control of both proliferation and apoptosis, was not affected by gamma-IFN. We conclude that gamma-IFN can suppress p53-induced apoptosis, and that the cytokine microenvironment may be decisive in the cellular response to wt p53 expression.
Sangfelt
O
O
Department of Oncology-Pathology, Karolinska Hospital and Institute, Stockholm, Sweden.
Einhorn
S
S
Björklund
A C
AC
Wiman
K G
KG
Okan
I
I
Grandér
D
D
D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma