Activation of Insulin-like Growth Factor I Receptor Signaling Pathway Is Critical for Mouse Plasma Cell Tumor Growth
2000
Plasma cell neoplasia in humans generally occurs as multiple myeloma, an
incurable form of cancer. Tumors with marked similarity can be induced
in mice by a variety of agents, including chemicals, silicone, and
oncogene-containing retroviruses, suggesting the use of murine tumors
as an informative model to study plasma cell disease. Herein, we have
focused on the role of insulin-like growth factor I receptor (IGF-IR)
signaling in the development of plasma cell disease. The insulin
receptor substrate 2/phosphatidylinositol 3′-kinase/p70S6K
pathway was found to be either constitutively or IGF-I-dependently
activated in all plasma cell tumors. Biological relevance was
demonstrated in that plasma cell lines with up-regulated IGF-IR
expression levels exhibited mitogenic responses to IGF-I. More
importantly, expression of a dominant-negative mutant of IGF-IR in
these lines strongly suppressed tumorigenesis in vivo .
Taken together, these results demonstrate that up-regulation and
activation of IGF-IR and the downstream signaling pathway involving
insulin receptor substrate 2, phosphatidylinositol 3′-kinase, and
p70S6K may play an important role in the development of a broad
spectrum of plasma cell tumors.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
44
References
26
Citations
NaN
KQI