Development of Human Prostate Cancer Stem Cells Involves Epigenomic Alteration and PI3K/AKT Pathway Activation
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.
Wu, J., Cang, S., Liu, C., Ochiai, W., & Chiao, J. (2020). Development of Human Prostate Cancer Stem Cells Involves Epigenomic Alteration and PI3K/AKT Pathway Activation. Experimental Hematology and Oncology, 9, 12-12. https://doi.org/10.1186/s40164-020-00168-0