Abstract
Cytoskeletal rearrangement occurs in variety of cellular processes and involves a wide spectrum of proteins. Gelsolin super family proteins control actin organization by severing and capping filament ends and nucleating actin assembly. Gelsolin is the founding member of this family and plays important role in pathogenesis of human neoplasia.This study aimed to investigate the germline mutations and expressional profile of Gelsolin in human breast cancer tissues. For germ line screening PCR-SSCP technique was used while expression was analyzed through quantitative real time PCR. Different types of mutations were observed in Gelsolin coding regions on exons 4, 10, 11, 14 and 15. These mutations include 3 missense nonsynonymous substitution mutations, 2 deletions, 1 insertion and 1 synonymous substitution mutation. Gelsolin transcript level was found significantly lower in breast tumor tissues compared to control samples (p=0.03). Low level of Gelsolin was found in metastatic patients (p=0.002) and patients who died from breast cancer (P=0.03) compared to disease free patients at final follow up. This study shows that level of Gelsolin is down regulated in breast cancer tissues and is linked with metastasis development and death in patients. It is concluded that genetic changes in coding regions of Gelsolin can potentially contribute to genetic instability. These genetic variations and expressional correlation with patient survival may prove to be of significant importance.
Highlights
Gelsolin protein super family is a conserved family of proteins present in mammalian and non-mammalian organisms [22]
General characteristic features associated with breast cancer were studied in patients (Table 1)
Multistage model of carcinogenesis proposes the growth of consecutive genetic abnormalities in oncogenes and tumor suppressor genes during tumor progression [45]
Summary
Gelsolin protein super family is a conserved family of proteins present in mammalian and non-mammalian organisms [22]. A protein of 82– 84 kDa, is the founding member of this family encoded by a gene on chromosome 9 It exists as a cytoplasmic as well as a plasma isoform and can bind, sever and cap actin filaments [21]. It is expressed in a wide variety of cell types and contains six gelsolin-like (G) domains. It was first described as a protein able to bind and sever actin filaments, and to control polymerization of barbed ends. Its expression in almost all eukaryotic cells shows its fundamental importance in maintaining an organized actin cytoskeleton [8,9]
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