NYMC Faculty Publications

Development of Human Prostate Cancer Stem Cells Involves Epigenomic Alteration and PI3K/AKT Pathway Activation

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Experimental Hematology and Oncology

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BACKGROUND: Human prostate cancer spheres endowed with stem cell properties have been obtained from androgen-dependent cell line LNCaP after exposure to an epigenomic modulator phenethyl isothiocynate (PEITC). Sphere cells can self-renew and grow with androgen, and also without androgen. Little is known about the signaling pathway and mechanism in the development of the stem cells in the spheres.

METHODS: Expression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting.

RESULTS: The level of phosphorylated AKT was significantly increased in the sphere stem cells than the LNCaP cells at an average of 7.4 folds (range 5.8-10.7 folds), whereas the P27 level was elevated 5.4 folds (range 4.8-6.3 folds) (

CONCLUSIONS: PEITC appears to regulate the epigenome through histone acetylation and activate the PI3K/AKT pathway in the LNCaP cells. This mechanism may be responsible in part for the development of the prostate cancer stem cells.

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