Article

Oncogene Functions of FHL2 Are Independent from NF-κBIα in Gastrointestinal Cancer

University of Hong Kong, Queen Mary Hospital Department of Medicine Hong Kong China
Pathology & Oncology Research (Impact Factor: 1.56). 03/2009; 15(1):31-36. DOI: 10.1007/s12253-008-9085-1

ABSTRACT Four and a half of LIM-only protein 2 (FHL2) is an adaptor protein that can interact with many transcription factors and thus
plays a variety of biological functions. Previous studies by our group have demonstrated that suppression of FHL2 was capable
of inducing tumor cell differentiation, and inhibiting the growth of experimental gastric and colon cancers. Therefore, FHL2
appears to function as an oncogene. In order to further explore the mechanisms of how FHL2 is involved in tumorigenesis, we
attempted to test whether FHL2 has any direct association with nuclear factor (NF-κB), the most important transcription factor
involved in apoptosis, inflammation, and carcinogenesis. Using an Yeast Two Hybrid (Y2H) screening system, we have shown that
FHL2 may have an interaction with NF-κBIα, the coding gene for IκBα which is the most potent endogenous inhibitor for NF-κB
activation. However, subsequent studies using co-immunoprecipitation and co-localization failed to confirm the Y2H finding.
Down-regulation of FHL2 by FHL2-siRNA down-regulated the expression of NF-κB p65. We therefore concluded that under the physiological
condition, FHL2 may activate NF-κB pathway, even though such an activation may not be mediated by a direct binding of FHL2
to NF-κB inhibitor protein IκB.

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