| 1. |
- Dubrovska, Anna, et al.
(författare)
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TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
- 2005
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 24:14, s. 2289-2297
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Tidskriftsartikel (refereegranskat)abstract
- Inactivation of the BRCA1 gene has been found to confer susceptibility to early-onset familial breast and ovarian cancers. BRCA1 regulates DNA repair, chromatin remodeling and affects gene transcription. Transforming growth factor-beta (TGFbeta) is a potent regulator of growth, apoptosis and invasiveness of tumor cells, including breast cancer cells. Here we show that Smad3 which is a component of the TGFbeta signaling pathway, forms a complex with BRCA1 in vitro and in vivo. The interaction is mediated by the MH1 domain of Smad3 and the C-terminal part of BRCA1. We observed a co-localization of Smad3 and BRCA1 in nuclear complexes. We also found that TGFbeta1/Smad3 counteracted BRCA1-dependent repair of DNA double-strand breaks in human breast epithelial cells, as evaluated by BRCA1 nuclear foci formation, single-cell gel electrophoresis and cell survival assays. Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent.
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| 2. |
- Lomnytska, Marta, et al.
(författare)
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Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:2, s. 412-421
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Tidskriftsartikel (refereegranskat)abstract
- Plasma samples of ovarian and breast cancer patients were used to search for markers of cancer using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. Truncated forms of cytosolic serine hydroxymethyl transferase (cSHMT), T-box transcription factor 3 (Tbx3) and utrophin were aberrantly expressed in samples from cancer patients as compared to samples from noncancerous cases. Aberrant expression of proteins was validated by immunoblotting of plasma samples with specific antibodies to cSHMT, Tbx3 and utrophin. A cohort of 79 breast and 39 ovarian cancer patients and 31 individuals with noncancerous conditions was studied. We observed increased expression of truncated cSHMT, Tbx3 and utrophin in plasma samples obtained from patients at early stages of disease. Our data suggest that cSHMT, Tbx3 and utrophin can be used as components of multiparameter monitoring of ovarian and breast cancer (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html).
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