Confirmation of the biological significance of transthyretin as a biomarker for cutaneous T-cell lymphoma by its protein interaction partners

Abstract

Abstract. We previously identified transthyretin (TTR) and its posttranslational modifications as a down-regulated marker in mycosis fungoides (MF), a benign subtype of cutaneous T-cell lymphoma (CTCL). In order to more precisely understand the biological role of TTR in the etiology of MF, it is essential to clarify the pathways of progression by identifying further interacting proteins. This study is the first to combine blue native polyacrylamide gel electrophoresis (BN-PAGE) with surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to detect new TTR interaction partners and to determine whether these TTR interaction partners can themselves be used as biomarkers. By this procedure, apolipoprotein A1, which was additionally found to be down-regulated in the serum of MF patients, apolipoprotein A4, retinol binding protein 4 (RBP-4), and retinoid X receptor β (RXR-β) were identified as interaction partners of TTR. The RXR family plays a role in cell differentiation and proliferation and is known to be the target of bexarotene, which is used in the treatment of CTCL. In conclusion, the combination of BN-PAGE and SELDI-TOF-MS used in this study allowed for the detection of protein interaction partners, which, in the case of RBP-4 and RXR, indicated a connection between the common tumor marker TTR and tumor progression in CTCL.

Effect and Mechanism of Transthyretin Over-Expression on Proliferation and Cell Cycle of Lung Cancer A549 Cells

“…As early as 2005, Schweigert and Sehouli found that TTR levels in serum of patients with early OC markedly changed ( 18 ).The levels in serum and ascites of OC patients were dramatically different ( 19 ). The differential expression of TTR had important biological significance in the development of cutaneous T-cell lymphoma ( 20 ). Katare et al found four mutations of TTR gene in LC rats, which changed three amino acids at positions 61, 100 and 115 ( 21 ).…”