Abstract
BackgroundHuman 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.MethodsExpression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting.ResultsThe 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.ConclusionsPEITC 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.
Highlights
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)
In an earlier study we identified prostate cancer stem cells (PSC) that form spheres in a cell culture system mimicking the evolving process of prostate tumors from an androgen-dependent to androgen-independent state [7]
Cell cycle and histone acetylation in prostate cancer stem cells To investigate the mechanisms involved in the PSC sphere formation, the status of cellular proliferation of the sphere cells was first examined
Summary
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). Little is known about the signaling pathway and mechanism in the development of the stem cells in the spheres. Prostate cancer remains a worldwide challenge, in the developed countries with increased screening [1,2,3]. Androgen-dependent prostate cancer recurs when the residual cells become androgen-independent and hormone refractory [4,5,6]. In an earlier study we identified prostate cancer stem cells (PSC) that form spheres in a cell culture system mimicking the evolving process of prostate tumors from an androgen-dependent to androgen-independent state [7]. The spheres were isolated from the androgen-dependent LNCaP cell culture.
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