Transforming growth factor beta (TGF−ss) signaling via Smads plays a central role in carcinogenesis. Bmp and activin membrane−bound inhibitor (BAMBI) was initially described as a pseudoreceptor antagonizing TGF−ss receptor activation, thus impairing signaling. Here we wanted to estimate the role of BAMBI in ovarian cancer.

The function of BAMBI was studied using a cell line model and intracellular localization experiments. The impact of BAMBI expression on patient outcome was estimated by real−time PCR and immunohistochemistry.

We demonstrate for the first time a nuclear co−translocation of BAMBI with Smad2/3 upon TGF−ss treatment. Moreover, overexpression of BAMBI in an in vitro model led to significantly increased proliferation (doubling time −37.0%, P=0.010), migration (+581.2%, P=0.004) and resistance to TGF−ss−mediated apoptosis (decrease of apoptosis from 30% in the control cells to 7% in the BAMBI−overexpressing cells). Although−prima facie−this fits to the thesis of BAMBI as a pseudoreceptor, it may also be explained by modulation of TGF−ss signaling in the nucleus, leading to the observed pro−oncogenic properties. The tumor promoting impact of BAMBI mRNA overexpression in vitro could not be confirmed in primary tumor samples, and while nearly all tumor samples showed up−regulation of BAMBI (37.3% 1+, 39.2% 2+, and 16.7% 3+, respectively) compared to undetectable BAMBI in healthy pre− and post−menopausal ovarian epithelia, no impact of BAMBI expression on recurrence free and overall survival could be observed.

These findings provide new insights into the Smad−mediated pathway by inferring that BAMBI is a novel modulator of TGF−ss signaling. Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20189233 [PubMed − as supplied by publisher] Source: National Library