TY  - JOUR
A1  - Wiegering, Armin
A1  - Pfann, Christina
A1  - Uthe, Friedrich Wilhelm
A1  - Otto, Christoph
A1  - Rycak, Lukas
A1  - Mäder, Uwe
A1  - Gasser, Martin
A1  - Waaga-Gasser, Anna-Maria
A1  - Eilers, Martin
A1  - Germer, Christoph-Thomas
T1  - CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression
JF  - PLoS ONE
N2  - The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.
KW  - caco-2 cells
KW  - carcinomas
KW  - colon
KW  - colorectal cancer
KW  - MAPK signaling cascades
KW  - metastasis
KW  - protein expression
KW  - small interferring RNA
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97252
ER  - 
TY  - JOUR
A1  - Becker, Svetlana
A1  - Oelschlaeger, Tobias A.
A1  - Wullaert, Andy
A1  - Pasparakis, Manolis
A1  - Wehkamp, Jan
A1  - Stange, Eduard F.
A1  - Gersemann, Michael
T1  - Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo
JF  - PLoS ONE
N2  - Background: The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell. 
Methods: Expression of the transcription factors Hes1, Hath1 and KLF4, the mucins Muc1 and Muc2 and the defensin HBD2 were measured by real-time PCR in LS174T cells following incubation with several heat-inactivated E. coli strains, including the probiotic E. coli Nissle 1917+/- flagellin, Lactobacilli and Bifidobacteria. For protein detection Western blot experiments and chamber-slide immunostaining were performed. Finally, mRNA and protein expression of these factors was evaluated in the colon of germfree vs. specific pathogen free vs. conventionalized mice and colonic goblet cells were counted. 
Results: Expression of Hes1 and Hath1, and to a minor degree also of KLF4, was reduced by E. coli K-12 and E. coli Nissle 1917. In contrast, Muc1 and HBD2 expression were significantly enhanced, independent of the Notch signalling pathway. Probiotic E. coli Nissle 1917 regulated Hes1, Hath1, Muc1 and HBD2 through flagellin. In vivo experiments confirmed the observed in vitro effects of bacteria by a diminished colonic expression of Hath1 and KLF4 in specific pathogen free and conventionalized mice as compared to germ free mice whereas the number of goblet cells was unchanged in these mice. 
Conclusions: Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch.
KW  - stem cells
KW  - inflammatory-bowel-disease
KW  - Ileal Crohns-disease
KW  - coli nissel 1917
KW  - ulcreative colitis
KW  - escherichia coli
KW  - porphyromonas gingivalis
KW  - antimicrobial peptides
KW  - colorectal cancer
KW  - alpha defensins
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131168
VL  - 8
IS  - 2
ER  -