p53 negatively regulates expression of FoxM1.
The Forkhead box M1 (FoxM1) oncogenic transcription factor is overexpressed in a majority of human tumors. p53 is a transcription factor and a major tumor suppressor that is mutated in 50% of human cancers. In this study, we compared the levels of FoxM1 in normal BJ human fibroblasts, BJ fibroblasts with p53 knockdown and corresponding BJ immortal/oncogenic cell lines with inactivated p53. We found that partial deletion or inactivation of p53 in these cells leads to upregulation of FoxM1 expression. Similarly, p53 knockdown in several human cancer cell lines with wt-p53 led to upregulation of FoxM1 mRNA and protein expression, while induction of p53 by DNA-damage led to downregulation of FoxM1. These data suggest that p53 negatively regulates FoxM1 expression and therefore inactivation of p53 in tumors could partially explain the phenomenon of FoxM1 overexpression in human cancers.
Pandit
Bulbul
B
Halasi
Marianna
M
Gartel
Andrei L
AL
D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D000097869:Polo-Like Kinase 1; C107585:FOXM1 protein, human