FLT3'ün karaciğer kanserindeki rolü

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types and ithas a high mortality rate. Its high incidence is a consequence of lack ofbiomarkers that could track the progression of the disease. Identification of amarker, which involves in different stages of cancer progression, through fibrosisto HCC, would be a good candidate for diagnosis, prediction of prognosis andtargeted therapies. Therefore we decided to identify a novel marker for HCCs, toovercome these consequences. Previously our group has shown that oval cellmarker FLT3, a known hematopoetic stem cell marker and which is known to beconstitutively active in many of the leukemias, has a role in liver regeneration.Also our immunohistochemical analysis of cirrhotic liver tissues have shown thatFLT3 is expressed in liver injury. Therefore, we decided to analyze the role ofFLT3 in hepatocellular carcinogenesis. Expression analysis of FLT3 on mRNAand 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 celllines (HepG2, Hep3B, Hep40, Huh7, PLC/PRF/5, Mahlavu, Focus, Sk-Hep-1,Snu182, Snu387, Snu398, Snu423, Snu449, Snu475) was performed. Four ofthese cell lines (Snu182, Snu398, Huh7 and Hep40) were chosen due to theirdifferent expression levels of FLT3 and the functional role of FLT3 in HCCs wasassessed by blocking its activity by a small molecule inhibitor K-252aNocardiopsis sp.. Functional studies had shown that upon inhibitor treatment,subcellular localization of the protein was changed and its invasion ability in vitrowas impaired. Also nude mice xenografts had shown that upon inhibitor treatmenttumor forming ability of FLT3 expressing cells were highly diminished. Thereforewe suggest that FLT3 has a role in hepatocellular carcinogenesis and it might beanother link between liver regeneration and hepatocellular carcinogenesis