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Cyclic AMP response element binding protein (CREB) regulation by asbestos
Author(s) -
Shukla Arti,
Barrett Trisha F,
Barlow Christy A,
Lounsbury Karen M,
Mossman Brooke T
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a180-c
Subject(s) - creb , asbestos , phosphorylation , cancer research , biology , microbiology and biotechnology , chemistry , gene , transcription factor , biochemistry , materials science , metallurgy
Inhalation of asbestos fibers has been associated with the development of lung cancers and mesotheliomas. Little is known about the crucial cellular mechanisms that initiate and drive the processes of carcinogenesis. Because CREs (Ca 2+ /cAMP response elements) are found in the promoters of many genes regulating proliferation and apoptosis, CREB (CRE binding protein) is likely to play an important role in asbestos‐induced diseases. Here we hypothesized that asbestos upregulates CREB and CREB‐regulated genes which could be responsible for increased cell survival. Exposure of lung epithelial type II cells (C10) to crocidolite asbestos led to rapid CREB phosphorylation that was dramatically decreased by inhibition of PKA or ERK1/2 using H89 and U0126, respectively. Telomerase‐immortalized human mesothelial cells (LP9) also showed rapid asbestos‐induced CREB phosphorylation that was inhibited by PKA inhibition but not by ERK1/2 or calmodulin kinase II inhibitors. CREB‐regulated genes ( egr‐1, mkp1, bcl2 ) also showed increases after asbestos exposure. Two mesothelioma cell lines (ME26 and ME27) showed significantly increased basal levels of CREB phosphorylation. CREB‐regulated bcl2 gene expression was elevated in both cell lines, whereas mkp1 was decreased. Our observations suggest that CREB likely plays an important role in asbestos‐induced cell survival. Supported by PO1HL67004, PO1CA11407 and T32ES0071.