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pten suppression on rheb expression through inhibition of mtorc1 s6k1 dependent protein translation in prostate cancer cells
2018
1. Abstract 1.1. Purpose: PTEN loss-of-expression and increase of
the RHEB protein are frequent oncogenic events in prostate cancer cells. The
aim of this study was to elucidate if loss of PTEN leads to the amplification
of the RHEB protein in prostate cancer cells. 1.2. Materials and Methods: The expression
levels of PTEN and RHEB in 2 cell lines (PC-3, and DU 145) 5 pairs of normal
prostatic epithelia and prostate tumor samples by real-time quantitative PCR
and western blot hybridization. 1.3. Results: The RHEB protein level was high in the
PC-3 cell line (PTEN-null) and low in the DU 145-cell line (PTEN-expressed).
The protein level, but not the mRNA level, of RHEB was up-regulated by PTEN
knockdown in DU 145 cells. The increased protein level of RHEB was observed in
5 tumor sample accompanied by decreased protein level of PTEN in 4 paired
normal tissues. Inhibitors of PI3K or mTORC1 interrupting the
PI3K/AKT1/mTORC1/S6K1 kinase cascade lowered the RHEB protein level in PC-3
cells. The upregulation of the RHEB protein in PTEN-knockdown DU 145 cells was
neutralized by inhibition of the PI3K/AKT1/mTORC1/S6K1 kinase cascade or the
subsequent protein translation. 1.4. Conclusions: These data suggested that the
antagonism of PTEN to the PI3K/AKT1 axis leads to the inhibition of the
mTORC1/S6K1-mediated protein translation, resulting in the decrease in the RHEB
protein level in prostate cancer cells. Our finding provided a new explanation
for the aberrant amplification of the RHEB protein in prostate cancer cells. 2. Keywords: mTORC1 Complex
Human; Prostate Cancer; PTEN Protein Human; Protein Translation RHEB Protein
Human
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