Abstract：
BACKGROUND:The tumour suppressor gene 'mutated in colorectal cancer' (MCC) is silenced through promoter methylation in colorectal cancer and has been implicated as a regulator of the nuclear factor kappa B (NFκB) pathway. Therefore, we aimed to determine whether MCC modulates NFκB activation in colorectal cancer. MATERIALS AND METHODS:NFκB activation was assessed using luciferase reporter assays in colorectal cancer cells in vitro. MCC methylation was analysed in primary tumour specimens from patients with inflammatory bowel disease. RESULTS:Re-expression of MCC reduced NFκB-dependent transcription in tumour necrosis factor alpha (TNFα)- or lipopolysaccharide (LPS)-stimulated cells. Conversely, knockdown of MCC resulted in accumulation of the inhibitor of kappa B alpha (IκBα) protein, encoded by NFKBIA, a first response gene specifically and rapidly regulated by NFκB pathway activation. The MCC gene is methylated in up to 6/16 of inflammatory bowel disease-associated tissue specimens, and myosin-10 and valosin-containing protein were identified as MCC-interacting proteins. CONCLUSION:These findings suggest that MCC modulates NFκB pathway signalling indirectly in colorectal cancer cells.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Sigglekow ND,Pangon L,Brummer T,Molloy M,Hawkins NJ,Ward RL,Musgrove EA,Kohonen-Corish MRsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
73-9issue
1eissn
0250-7005issn
1791-7530pii
32/1/73journal_volume
32pub_type
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doi：
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