Localization of recognition site between transforming growth factor- (TGF-) and TGF receptor type II: possible implications in breast cancer

Autor: D Nikolic-Vukosavljevic, Miroslav Demajo, Koviljka Krtolica, Vesna Ivanovic, Nataša Todorović-Raković, Bogomir Dimitrijević, Veljko Veljkovic, Z Neskovic-Konstantinovic, J Prljić
Rok vydání: 2004
Předmět:
Zdroj: Medical Hypotheses. 62:727-732
ISSN: 0306-9877
DOI: 10.1016/j.mehy.2003.11.027
Popis: Although overexpression of TGF-β 1 protein has been demonstrated in advanced breast cancer(BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-β 1 gene, within the region coding for the recognition site with TGFβ receptor type II, leading to a disruption of the ligand–receptor interaction and triggering the TGF-β 1 cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-β 1 peptides (positions 47–66 aa and 83–112 aa) and one receptor peptide at positions 112–151 aa of the extracellular domain of the receptor (TβRII M ). The TβRII M locus was further evaluated by ISM-derived deletion analysis of the TβRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-β 1 analysis was performed in advanced BC patients ( n =8). Two commercial ELISA assays, one with specific αTGF-β 1 MAb (MAb) and other with TβRII M as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-β 1 elevation. In MAb-profile, the TGF-β 1 increase was detected in 7 of 8 patients, whereas analogous TβRII M -profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-β 1 ligand within the TβRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-β 1 and TβRII M interaction, with putative prognostic value for breast cancer.
Databáze: OpenAIRE
Externí odkaz: