Study On The Mechanism Of Transcriptional Factor Apt In Suppressing Tumor Proliferation And Metastasis In Drosophila

As we know,malignant tumor,also known as cancer,as one of killer of human health,has become a problem that should be handled by scientific and medical community of the world.According to the data of WHO,there are about 20 million people are affected with cancer,with 9.6 million of them dying of cancer.In 2040,individuals dying of cancer will up to 17 million.High death rate and low cure rate of cancer have made people scared.So it is urgent to overcome cancer.Over the past decades,drosophila melanogaster has become a very important model to study cancer,and it has contributed greatly to the understanding of genetics and development of cancer.In drosophila,lgl is a cell polarity factor,also known as tumor suppressor,can develop into tumor after being mutated.Because of cell competence,these tumor tissue will be removed easily.Ras is an oncogene,as in vertebrate,it can promote the growth,survive and proliferation of the cell.lgl and Ras can have an oncogenic corporation,and those tumors appear the same characters as human tumor.This technique was named as Mosaic analysis with a Repressible Cell Marker?MARCM?,this technique promotes the development of tumor research deeply.This project studies a transcription factor Apt,to see the influence of it on tumorigenesis.Apt is an evolutionally conserved transcription factor,and FSBP is the homologue of it in mammal.First,we have built a tumor metastasis model using the technique of MARCM in drosophila.In this model,a tumor with the genotype of lgl^-/-/Ras^v12 can appear in the eyes of the larvae,with time going on,the tumor will grow up rapidly,invading Ventral Nerve Cord?VNC?and other sites of the body.If we over express Apt in tumor,the tumor will be smaller than before,and the transferring ability of it will decrease.According to the antibody stain and RT-qPCR experiment,Apt can suppress the activity of JNK in transcription and protein level.Nevertheless,knock down the expression of Apt using RNAi technique will have an operate result.As is reported before,the ability of tumor growth and invasion is related with JNK?cJun N-terminal Kinase?signaling pathway,whose activation will promote the growth and invasion of the tumor.According to the microarray data,Apt can regulate the JNK related genes,such as hep,puc,bsk and so on.Furthermore,overexpression of Apt has the same phenotype as overexpression of bsk^DN.These results indicating that Apt can regulate tumor growth and invasion by regulating the activity of Caspase 3,CyclinE and JNK signaling pathway.This study first show the function of Apt in tumor development.This study is very important to the research of tumor proliferation and invasion,and can also offer a theoretical guidance for cancer therapy.