Study On FoxA1Influenced Breast Cancer Cell Proliferation

Breast cancer is a heterogeneous disease and classification is important for clinicalmanagement. At least five subtypes can be identified based on unique gene expressionpatterns, this subtype classification is distinct from the histopathological classification. Thetranscription factor network(s) required for the specific gene expression signature in each ofthese subtypes. In luminal subtype A breast cancers, the transcription factor networkcomposed of the ERα (estrogen receptor α), FOXA1and GATA3may control the geneexpression pattern. Breast cancers that are dependent on this network correspond towell-differentiated and hormone-therapy-responsive tumours with good prognosis.The transcription factor FoxA1(Forkhead-box A1), a member of the FOX class oftranscription factors, has been implicated in the pathogenesis of lung, esophageal and prostatecancers. p21is currently known as a cell cycle inhibitor with broad kinase restraincompetence, it hampers the formation of cyclin-CDK complex and thereby negatively regμlates the function of cyclin-dependent kinase（CDK）. p27is regarded as a tumor inhibitoryfactor and primarily inhibits the cyclin-CDK activity by binding to cell cycle protein（scyclin）.There are two ways that p27takes to inhibit CDK, one way is to restrain the activity of CDKswhich have combined to cyclin, the other way is to block the activation process of CDKs andμltimately inhibit the G1-S cell cycle transition.In this study, we constructed lentiviral vector that expresses FoxA1and FoxA1lentivirushas been successfμlly collected. By using FoxA1lentivirus and specific FoxA1siRNA inbreast cancer cells respectively, we found that the over expression of FoxA1represses the cellproliferation, while the knock down of FoxA1accelerates the proliferation. Further RT-PCRanalysis shows that increased mRNA levels of p21and p27are detected after the overexpression of FoxA1, which indicates FoxA1can activate the transcription activities of p21and p27. Resμlts from our study show that FoxA1, as a repressor of tumor growth, mayinhibit breast cancer cell proliferation by stimμlating the expression of p21and p27. Ourstudy may lead us to a new direction for gene therapy of breast cancer.