Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation

Experimental Hematology & Oncology
Jingjing WuJen Wei Chiao

Abstract

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. Expression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting. 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) (P < 0.05). The acetylation level on histone H3 lysine 9 was decreased. 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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Citations

Feb 14, 2021·Experimental Hematology & Oncology·Bing DongKongming Wu

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Methods Mentioned

BETA
histone acetylation
immunoprecipitation
electrophoresis
flow cytometry
acetylation

Software Mentioned

ProteinSimple

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