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Study of Kazal motifs of RECK protein on MMP-2 and MMP-9 activity and metastasis of lung adenocarcinoma

RECK stands for ¡¥reversion-inducing cysteine-rich protein with Kazal motifs¡¦. This gene was initially discovered by screening a human fibroblast cDNA library for genes giving rise to reversion-inducing clones when transfected into v-Ki-ras transformed NIH3T3 cells. The key action of RECK is to inhibit matrix metalloproteinases (MMPs), and it has a significant effect on limiting tumor invasion. Located within the middle part of RECK protein are three serine protease inhibitor-like (SPI) domains (635-654,716-735 and 754-772 amino acids, respectively) which are similar to Kazal motif. Kazal motif is a peptidase inhibitor motif containing disulfide bonds with small alpha and beta folds. The first of these SPI is identical to the Kazal motif (named as K1) and the other two SPIs are highly similar to the Kazal motif (named as K2 & K3). Given RECK is a MMP inhibitor, these SPI-like domains are likely to have a significant role in MMP inhibition.
Our previous data indicated that K23 motifs of RECK protein can inhibit MMP-9 secretion and activity and attenuate metastasis of lung cancer cells. To go a step further, we constructed secretory mammalian expression vectors which could produce K1, K2 and K3 to investigate their effect on MMP activity and cell invasion. We found that K2 also exhibited inhibitory activity on MMP activity and cell invasion. Thus, these finding indicate that the K2 domain of RECK function may be developed as a peptide inhibitor of tumor invasion.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0806109-130653
Date06 August 2009
CreatorsLiu, Yi-Jia
ContributorsLong-sen Chang, Wen-Chun Hung, Hui-Chiu Chang
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0806109-130653
Rightscampus_withheld, Copyright information available at source archive

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