Downstream Target Genes Of Homeotic Transcription Factor P150^sal2

p150^sal2, a homeotic transcription factor that can activate thetranscription of tumor suppressor gene p21, may play a role of tumorsuppression in tumorigenesis, a function similar to p53in the cell growthinhibition and induction of apoptosis. So we propose a hypothesis thatp150^sal2, along with activation of tumor suppressor genes, may alsoinhibit genes involved in development and differentiation of cells,including the genes expressed before onset of cancer. In addition to p21gene regulation, this study will focus on determining other tumorigenesisrelated downstream target genes and their regulatory mechanisms thatmay be controlled by p150^sal2.In this study, microarray analysis of p150^sal2downstream regulatorychannel was performed for the expression analysis of spectrum of morethan forty thousand genes and constructed the promoters of the genessuch as p16INK4A, p27, c-Jun, c-Myc, etc that were regulated by p150^sal2 and closely related to tumorigenesis, and were detected usingdual-luciferase reporter gene detection method. According to the resultthat p150^sal2will increase the expression of p16, we constructed a seriesof mutants of p16promoter, and co-transfected with p150^sal2 intoSKOV3cells. We found that p150^sal2in combination with p16promotercis-acting element, regulates the p16expression. Western blot was used toverify that p150^sal2induces the expression of p16in the cell, and flowcytometry was used to detect the changes in the cell cycle and inhibitionof cell access into the G2/M phase after the promotion of p16expression.Our results reveal that p150^sal2, a development-related transcriptionfactor, can directly regulate p53and pRb, the two key signaling pathways,rendering them as new candidate targets of anticancer drug screening.