| Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 94 === Insulin-like growth factors (IGF-I and IGF-II) are the major growth
promoting growth factors in the circulation system. These ligands
stimulate cell survival and promote proliferation and differentiation of
different cell types. IGF is also related to cancer formation. It might
induce proliferation and anti-apoptosis in cancer cells. Thereby, blockage
of IGF has been tested for an anti-cancer regimen. There are six IGFBPs
in IGFBP gene family. IGFBPs prolong half-life of the IGFs in the
circulation and inhibit their metabolic effects by preventing them from
binding to their receptors. IGFBP-5 also exhibit IGF-independent action
that might drive variable effects. Controversial phenotypic impacts of
IGFBP-5 against different types of cells were shown. The discrepancies
in phenotypic impacts may be resulted from the differential influences
from IGF-dependent and IGF-independent functions. Previously, our
laboratory has found that IGFBP-5 could inhibit OECM-1 and SAS oral
cancer cell proliferation and promote theirs migration. However, such
regulation is IGF-dependent or IGF-independent needs further
clarification. In this study, I plan to distinguish the IGF-dependent and
IGF-independent cellular impacts in oral cancer cells using mutation
constructs. I generated a mutant construct that disrupts IGF binding site, a
construct with N-terminal deletion and vector alone plasmid. Transient
transfection and comparison analysis indicated that the deletion construct
enhance cell proliferation indicating and existence of domains other than
IGF-binding site lie in N terminal that against growth. Besides, the
induction of cell migration ability mediated by IGFBP-5 was
IGF-dependent.
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