Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer
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Аутори
Ivanović, VesnaDemajo, Miroslav
Todorović-Raković, N
Nikolić-Vukosavljević, Dragica
Nešković-Konstantinović, Zora
Krtolica-Žikić, Koviljka
Veljković, Veljko
Prljić, Jelena
Dimitrijević, Bogomir B.
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Although overexpression of TGF-beta(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-beta(1) gene, within the region coding for the recognition site with TGF(beta) receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta(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-beta(1) peptides (positions 47-66 as and 83-112 aa) and one receptor peptide at positions 112-151 as of the extracellular domain of the receptor (TbetaRII(M)). The TbetaRII(M) locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model..., a pilot study of plasma TGF-beta(1) analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta(1) MAb (MAb) and other with TbetaRII(M) as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta(1) elevation. In MAb-profile, the TGF-beta(1) increase was detected in 7 of 8 patients, whereas analogous TbetaRII(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-beta(1) ligand within the TbetaRII 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-beta(1) and TbetaRII(M) interaction, with putative prognostic value for breast cancer. (C) 2004 Elsevier Ltd. All rights reserved.
Извор:
Medical Hypotheses, 2004, 62, 5, 727-732
DOI: 10.1016/j.mehy.2003.11.027
ISSN: 0306-9877
PubMed: 15082097
WoS: 000221376900016
Scopus: 2-s2.0-2142696747
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VinčaTY - JOUR AU - Ivanović, Vesna AU - Demajo, Miroslav AU - Todorović-Raković, N AU - Nikolić-Vukosavljević, Dragica AU - Nešković-Konstantinović, Zora AU - Krtolica-Žikić, Koviljka AU - Veljković, Veljko AU - Prljić, Jelena AU - Dimitrijević, Bogomir B. PY - 2004 UR - https://vinar.vin.bg.ac.rs/handle/123456789/2769 AB - Although overexpression of TGF-beta(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-beta(1) gene, within the region coding for the recognition site with TGF(beta) receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta(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-beta(1) peptides (positions 47-66 as and 83-112 aa) and one receptor peptide at positions 112-151 as of the extracellular domain of the receptor (TbetaRII(M)). The TbetaRII(M) locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta(1) analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta(1) MAb (MAb) and other with TbetaRII(M) as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta(1) elevation. In MAb-profile, the TGF-beta(1) increase was detected in 7 of 8 patients, whereas analogous TbetaRII(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-beta(1) ligand within the TbetaRII 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-beta(1) and TbetaRII(M) interaction, with putative prognostic value for breast cancer. (C) 2004 Elsevier Ltd. All rights reserved. T2 - Medical Hypotheses T1 - Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer VL - 62 IS - 5 SP - 727 EP - 732 DO - 10.1016/j.mehy.2003.11.027 ER -
@article{ author = "Ivanović, Vesna and Demajo, Miroslav and Todorović-Raković, N and Nikolić-Vukosavljević, Dragica and Nešković-Konstantinović, Zora and Krtolica-Žikić, Koviljka and Veljković, Veljko and Prljić, Jelena and Dimitrijević, Bogomir B.", year = "2004", abstract = "Although overexpression of TGF-beta(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-beta(1) gene, within the region coding for the recognition site with TGF(beta) receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta(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-beta(1) peptides (positions 47-66 as and 83-112 aa) and one receptor peptide at positions 112-151 as of the extracellular domain of the receptor (TbetaRII(M)). The TbetaRII(M) locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta(1) analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta(1) MAb (MAb) and other with TbetaRII(M) as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta(1) elevation. In MAb-profile, the TGF-beta(1) increase was detected in 7 of 8 patients, whereas analogous TbetaRII(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-beta(1) ligand within the TbetaRII 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-beta(1) and TbetaRII(M) interaction, with putative prognostic value for breast cancer. (C) 2004 Elsevier Ltd. All rights reserved.", journal = "Medical Hypotheses", title = "Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer", volume = "62", number = "5", pages = "727-732", doi = "10.1016/j.mehy.2003.11.027" }
Ivanović, V., Demajo, M., Todorović-Raković, N., Nikolić-Vukosavljević, D., Nešković-Konstantinović, Z., Krtolica-Žikić, K., Veljković, V., Prljić, J.,& Dimitrijević, B. B.. (2004). Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer. in Medical Hypotheses, 62(5), 727-732. https://doi.org/10.1016/j.mehy.2003.11.027
Ivanović V, Demajo M, Todorović-Raković N, Nikolić-Vukosavljević D, Nešković-Konstantinović Z, Krtolica-Žikić K, Veljković V, Prljić J, Dimitrijević BB. Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer. in Medical Hypotheses. 2004;62(5):727-732. doi:10.1016/j.mehy.2003.11.027 .
Ivanović, Vesna, Demajo, Miroslav, Todorović-Raković, N, Nikolić-Vukosavljević, Dragica, Nešković-Konstantinović, Zora, Krtolica-Žikić, Koviljka, Veljković, Veljko, Prljić, Jelena, Dimitrijević, Bogomir B., "Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer" in Medical Hypotheses, 62, no. 5 (2004):727-732, https://doi.org/10.1016/j.mehy.2003.11.027 . .