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Forkhead box M1 (FoxM1) gene is a new STAT3 transcriptional factor target and is essential for proliferation, survival and DNA repair of K562 cell line.

ABSTRACT: The forkhead box (Fox) M1 gene belongs to a superfamily of evolutionarily conserved transcriptional regulators that are involved in a wide range of biological processes, and its deregulation has been implicated in cancer survival, proliferation and chemotherapy resistance. However, the role of FoxM1, the signaling involved in its activation and its role in leukemia are poorly known. Here, we demonstrate by gene promoter analysis, Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays that FoxM1 is a new target of the STAT3 transcriptional activator. Additionally, FoxM1 is transcriptionally dependent on STAT3 signaling activation. Furthermore, we verified that FoxM1 is crucial for K562 cell proliferation, cell cycle checkpoints and viability and could be related to chemotherapeutic resistance. By microarray analysis, we determined the signaling pathways related to FoxM1 expression and its role in DNA repair using K562 cells. Our results revealed new signaling involved in FoxM1 expression and its role in leukemic cells that elucidate cellular mechanisms associated with the development of leukemia and disease progression.

SUBMITTER: Mencalha AL

PROVIDER: S-EPMC3480485 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Forkhead box M1 (FoxM1) gene is a new STAT3 transcriptional factor target and is essential for proliferation, survival and DNA repair of K562 cell line.

Mencalha André L AL Binato Renata R Ferreira Gerson M GM Du Rocher Barbara B Abdelhay Eliana E

PloS one 20121024 10

The forkhead box (Fox) M1 gene belongs to a superfamily of evolutionarily conserved transcriptional regulators that are involved in a wide range of biological processes, and its deregulation has been implicated in cancer survival, proliferation and chemotherapy resistance. However, the role of FoxM1, the signaling involved in its activation and its role in leukemia are poorly known. Here, we demonstrate by gene promoter analysis, Electrophoretic mobility shift assay (EMSA) and chromatin immunopr ...[more]

PMID: 23110199

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Project description:The composition of the prostate microbiome may influence the fate of the cells that may be relevant to prostate morbidity. Several independent studies have reported the presence of the bacterium Propionibacterium acnes in diseased human prostate tissue. It is unclear if the bacterium is an infectious agent, part of a normal prostate microbiota or if it is derived from the skin and accidentally introduced, for instance during a prostate biopsy. Previous research with prostate cell culture and animal models has revealed the capability of P. acnes to establish a low-grade chronic inflammation. However, the fate of primary prostate cells exposed to P. acnes has not been investigated in molecular detail. Here, we investigated the impact of P. acnes on human primary prostate epithelial cells (PrEC). An initial analysis of the host cell response by microarray technology confirmed the inflammation-inducing capability of P. acnes but also showed the deregulation of genes involved in cell cycle, and more specifically in kinetochore and centromere functionality. In particular, we could show and confirm by qPCR that only viable P. acnes downregulated a master regulator of cell cycle progression, FOXM1, as well as its target genes. It was further shown by flow cytometry that P. acnes was indeed able to alter the cell cycle by increasing the number of PrEC cells in S-phase. In search for a molecular explanation we tested the hypothesis that a P.acnes produced berninamycin A-like thiopeptide, that is a structurally closely related to the known FOXM1 inhibitor siomycin A, is responsible for the effect on FOXM1 and the cell cycle. A knock-out mutant in P. acnes was created that lacked the gene encoding the berninamycin A peptide precursor; this mutant was unable to downregulate FOXM1, suggesting that a berninamycin A-like thiopeptide induces cell cycle alterations in PrEC cells. Interestingly, the gene cluster encoding this thiopeptide is restricted to a subtype of P. acnes that is relatively rare on human skin, but more often found in prostate tissue.

Dataset Information

Forkhead box M1 (FoxM1) gene is a new STAT3 transcriptional factor target and is essential for proliferation, survival and DNA repair of K562 cell line.

Publications

Forkhead box M1 (FoxM1) gene is a new STAT3 transcriptional factor target and is essential for proliferation, survival and DNA repair of K562 cell line.

Similar Datasets

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