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  - Djuzenova, Cholpon S.
A1  - Zimmermann, Marcus
A1  - Katzer, Astrid
A1  - Fiedler, Vanessa
A1  - Distel, Luitpold V.
A1  - Gasser, Martin
A1  - Waaga-Gasser, Anna-Maria
A1  - Flentje, Michael
A1  - Polat, Bülent
T1  - A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome
JF  - BMC Cancer
N2  - Background
The prognostic value of histone γ-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone γ-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor.

Methods
Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references.

Results
The γ-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients.

Conclusions
The study shows higher expression of γ-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome.
KW  - radiosensitivity
KW  - peripheral blood lymphocytes
KW  - DNA repair
KW  - DNA damage
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125303
VL  - 15
IS  - 856
ER  -