Browsing by Subject "FLT3"

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Open Access
Cloning and expression profile of FLT3 gene during progenitor cell-dependent liver regeneration
(Blackwell Publishing, 2007) Aydin, I. T.; Tokcaer, Z.; Dalgic, A.; Konu, O.; Akcali, K. C.
Background and Aim: The liver has a unique capacity to regenerate upon exposure to viral infections, toxic reactions and cancer formation. Liver regeneration is a complex phenomenon in which several factors participate during its onset. Cellular proliferation is an important component of this process and the factors that regulate this proliferation have a vital role. FLT3, a well-known hematopoietic stem cell and hepatic lineage surface marker, is involved in proliferative events of hematopoietic stem cells. However, its contribution to liver regeneration is not known. Therefore, the aim of this study was to clone and examine the role of FLT3 during liver regeneration in rats. Methods: Partial cDNA of rat homolog of FLT3 gene was cloned from thymus and the tissue specific expression of this gene at mRNA and protein levels was examined by RT-PCR and Western blot. After treating with 2-AAF and performing hepatectomy in rats to induce progenitor-dependent liver regeneration, the mRNA and protein expression profile of FLT3 was investigated by real-time PCR and Western blot during liver regeneration. In addition, cellular localization of FLT3 protein was determined by immunohistochemistry. Results: The results indicated that rat FLT3 cDNA has high homology with mouse and human FLT3 cDNA. It was also found that FLT3 is expressed in most of the rat tissues and during liver regeneration. In addition, its intracellular localization is altered during the late stages of liver regeneration. Conclusion: The FLT3 receptor is activated at the late stages of liver regeneration and participates in the proliferation response that is observed during progenitor-dependent liver regeneration. © 2006 The Authors.
Open Access
Cloning and expression profile of FLT3 gene during rat liver regeneration
(2005) Aydın, Iraz Toprak
Liver has a unique capacity to regenerate itself upon exposure to viral infections, toxic reactions and cancer formation which result in the loss of hepatocyte. Liver regeneration is a complex phenomenon in which several factors participate during its onset. Cellular proliferation is one of the important component of this process and the factors regulate this proliferation has a vital role. FLT3, a well-known hematopoietic stem cell and hepatic lineage surface marker, takes place in proliferative events of hematopoietic stem cells. However, its contribution to liver regeneration is not known. Therefore, in this study, we aimed to examine the role of FLT3 during liver regeneration. First we cloned a partial cDNA of rat homolog of FLT3 from thymus and examined the tissue specific expressions both in mRNA and protein level. After performing hepatectomy in rats to induce liver regeneration, expression profile of FLT3 in both mRNA and protein level and its cellular localization were also investigated during the different stages of liver regeneration models. Our data showed that FLT3 is expressed in most of the rat tissues and in liver regeneration. However, its intracellular localization is changed during the late stages of liver regeneration. Therefore, our results suggest a mechanism in which FLT3 receptor is activated in the late stages of liver regeneration.
Open Access
The role of FLT3 in hepatocellular carcinogenesis
(2010) Bayın, N. Sumru
Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types and it has a high mortality rate. Its high incidence is a consequence of lack of biomarkers that could track the progression of the disease. Identification of a marker, which involves in different stages of cancer progression, through fibrosis to HCC, would be a good candidate for diagnosis, prediction of prognosis and targeted therapies. Therefore we decided to identify a novel marker for HCCs, to overcome these consequences. Previously our group has shown that oval cell marker FLT3, a known hematopoetic stem cell marker and which is known to be constitutively active in many of the leukemias, has a role in liver regeneration. Also our immunohistochemical analysis of cirrhotic liver tissues have shown that FLT3 is expressed in liver injury. Therefore, we decided to analyze the role of FLT3 in hepatocellular carcinogenesis. Expression analysis of FLT3 on mRNA and protein level and the expression analysis of adult stem cell, cancer stem cell, and epithelial and mesenchymal lineage markers on mRNA level in 14 HCC cell lines (HepG2, Hep3B, Hep40, Huh7, PLC/PRF/5, Mahlavu, Focus, Sk-Hep-1, Snu182, Snu387, Snu398, Snu423, Snu449, Snu475) was performed. Four of these cell lines (Snu182, Snu398, Huh7 and Hep40) were chosen due to their different expression levels of FLT3 and the functional role of FLT3 in HCCs was assessed by blocking its activity by a small molecule inhibitor K-252a Nocardiopsis sp.. Functional studies had shown that upon inhibitor treatment, subcellular localization of the protein was changed and its invasion ability in vitro was impaired. Also nude mice xenografts had shown that upon inhibitor treatment tumor forming ability of FLT3 expressing cells were highly diminished. Therefore we suggest that FLT3 has a role in hepatocellular carcinogenesis and it might be another link between liver regeneration and hepatocellular carcinogenesis.
Open Access
Therapeutic approaches to the prevention of liver fibrosis and cancer progression
(2015-08) Aydın, Muammer Merve
In our previous studies on liver regeneration, we demonstrated that following partial hepatectomy (PH) FLT3 contributes cellular proliferation that provides a basis for liver regeneration. Moreover, we were able to suggest a potential role for FLT3 in hepatocarcinogenesis for the first time. Therefore, we further investigated the effect of FLT3 inhibition on the invasiveness and aggressiveness of hepatocarcinogenesis. Our findings were parallel to our previous results supporting the contribution of FLT3 in hepatocarcinogenesis. Thus, we are presenting FLT3 as a novel candidate for the diagnosis and treatment of HCC. We also focused on liver fibrosis since it is the initial wound healing response generated by the liver against damaging insults. Liver fibrosis is a reversible process, but if its progression is not prevented it might turn into cirrhosis and end up with HCC. Toll-like receptors (TLRs) have been reported to contribute to this fibrotic response generated in the liver resulting from the activating effects of various danger ligands. We show that using suppressive oligodeoxynucleotide (ODN) A151 might control TLR dependent immune activation that takes place after the induction of liver fibrosis. Our results show that suppressive ODN A151 administration has a negative effect on αSMA expression and collagen accumulation, which are the major events taking place during liver fibrogenesis. Additionally, this suppressive effect of suppressive ODN A151 was revealed to be systemic. Splenocytes of suppressive ODN A151 administered mice showed different cytokine secretion patterns and antigen presenting cell (APC) function after being stimulated with various TLR ligands. These findings suggested us that using suppressive ODN might be a rational and novel approach to control the liver fibrogenesis and even prevent its progression into cirrhosis reducing the number of liver transplantations needed by the patients. Finally, we focused on HSPs, some of which are also known to activate TLR signaling. Additionally, HSP27 has a role in actin cytoskeleton organization and controlling cellular motility, which are among the events that take place in liver fibrogenesis. Therefore, for the first time we present preliminary data on the potential role of HSP27 in liver fibrosis and quercetin treatment as a therapeutic approach due to its HSP27 and αSMA expression changing effects.