Biomedical Engineering Reference
In-Depth Information
large cell lymphoma [38]. KIF5B is a component of a motor protein
complex that is associated with microtubules and mediates the
transport of organelles within eukaryotic cells. Similar to EML4, both
TFG and KIF5B have dimerization domains near the amino-terminal
end necessary for malignant transformation. The presence of these
non-EML4 partners for ALK has implications for the method used to
detect
rearrangements in NSCLC and the clinical significance of
these different fusions needs to be further explored.
ALK
Figure 16.3
Schematic representation of
EML4-ALK
translocations in
NSCLC [31].
16.2.5
The Transforming Activity of EML4-ALK
The oncogenic potential of
was confirmed by expression
in 3T3 fibroblasts that acquired the ability to grow as transformed
cell foci in culture [9]. Subcutaneous injections of the transfected
3T3 cells into nude mice also formed tumors [9]. On the contrary, the
EML4-ALK
EML4-ALK
kinase inactive mutants (K589M) in which Lys 589 in the
ATP-binding site of the kinase domain is replaced with Met, showed
no ability to form tumors thus confirming the catalytic activity of the
kinase domain as being essential.
in the pathogenesis of
NSCLC, transgenic mice specifically expressing the fusion protein
To further assess the role of
EML4-ALK
