Details

Autor(en) / Beteiligte

• Cutler, Samuel J.
• Doecke, James D.
• Ghazawi, Ibtisam
• Yang, Jinbo
• Mellick, Albert S.
• Ralph, Stephen J.

Titel

56: STAT-1 regulates constitutive and IL-6/PMA-inducible MMP-1 and MMP-3 expression in colorectal cancer via proximal promoter STAT binding elements

Ist Teil von

• Cytokine (Philadelphia, Pa.), 2013-09, Vol.63 (3), p.256-256

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2013

Link zum Volltext

Quelle

ScienceDirect Journals (5 years ago - present)

Beschreibungen/Notizen

• Interleukin-6 (IL-6) is a major regulator of matrix metalloproteinase (MMP) expression in cancers. A patient matched control study of human colorectal cancers revealed that levels of IL-6 expression correlated strongly with those of MMP-1 and MMP-3. In human colon cancer cell lines,MMP-3 expression was increased by treatment with IL-6, and suppressed by interferon-gamma (IFN-γ). Analysis of the MMP-1 and MMP-3 proximal promoters by gel shift and ChIP assays revealed noncanonical STAT binding elements (SBEs) which bound STAT-1 in a complex with AP-1/Fos constitutively and in an IL-6/PMA-inducible manner. STAT-3 was not observed to bind to these novel proximal promoter SBEs. Using northern blot analysis with a STAT-3 knockout colon cancer cell line confirmed that STAT-3 was not required for the IL-6 inducibility of MMP-1 and -3 expression. However, STAT-1 specific siRNA knockdown significantly inhibited induction, validating the requirement for STAT-1 in transcriptional activation. These results strengthen a role for STAT-1 in cytokine induction of malignancy-associated factors such as MMPs in colorectal cancer.