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Relevance and therapeutic possibility of PTEN-long in renal cell carcinoma.

Wang H, Zhang P, Lin C, Yu Q, Wu J, Wang L, Cui Y, Wang K, Gao Z, Li H - PLoS ONE (2015)

Bottom Line: We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt).When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage.Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Institute of Urology, Zhifu, Yantai, Shandong, 264000, People's Republic of China.

ABSTRACT
PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.

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Related in: MedlinePlus

Overexpression of PTEN-Long inhibits cell proliferation and induces cell death.A, Cell proliferation assay indicating reduced growth in 786-0 cells expressing PTEN or PTEN-Long compared to PTENG129R, PTEN-LongG302R, or empty vector transfected cells. B, AnnexinV staining followed by flow cytometry analysis indicating overexpression of PTEN or PTEN-Long promoted serum starvation-induced apoptosis.
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pone-0114250-g003: Overexpression of PTEN-Long inhibits cell proliferation and induces cell death.A, Cell proliferation assay indicating reduced growth in 786-0 cells expressing PTEN or PTEN-Long compared to PTENG129R, PTEN-LongG302R, or empty vector transfected cells. B, AnnexinV staining followed by flow cytometry analysis indicating overexpression of PTEN or PTEN-Long promoted serum starvation-induced apoptosis.

Mentions: PTEN has been reported to play a crucial role in modulating proliferation and apoptosis by reducing the levels of PIP3 that activates Akt, a central regulator of survival and death of cell. To understand the role of PTEN-Long in regulating cell proliferation and cell death, we stably overexpressed PTEN, PTENG129R, PTEN-Long or PTEN-LongG302R in 786-0 cells and compared their effects on cell growth and induction of cell death. We found, similar to PTEN, overexpression of PTEN-Long in 786-0 cells inhibited cell proliferation and this depends on its lipid phosphatase activity as PTEN-LongG302R showed no effect (Fig. 3A).


Relevance and therapeutic possibility of PTEN-long in renal cell carcinoma.

Wang H, Zhang P, Lin C, Yu Q, Wu J, Wang L, Cui Y, Wang K, Gao Z, Li H - PLoS ONE (2015)

Overexpression of PTEN-Long inhibits cell proliferation and induces cell death.A, Cell proliferation assay indicating reduced growth in 786-0 cells expressing PTEN or PTEN-Long compared to PTENG129R, PTEN-LongG302R, or empty vector transfected cells. B, AnnexinV staining followed by flow cytometry analysis indicating overexpression of PTEN or PTEN-Long promoted serum starvation-induced apoptosis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340966&req=5

pone-0114250-g003: Overexpression of PTEN-Long inhibits cell proliferation and induces cell death.A, Cell proliferation assay indicating reduced growth in 786-0 cells expressing PTEN or PTEN-Long compared to PTENG129R, PTEN-LongG302R, or empty vector transfected cells. B, AnnexinV staining followed by flow cytometry analysis indicating overexpression of PTEN or PTEN-Long promoted serum starvation-induced apoptosis.
Mentions: PTEN has been reported to play a crucial role in modulating proliferation and apoptosis by reducing the levels of PIP3 that activates Akt, a central regulator of survival and death of cell. To understand the role of PTEN-Long in regulating cell proliferation and cell death, we stably overexpressed PTEN, PTENG129R, PTEN-Long or PTEN-LongG302R in 786-0 cells and compared their effects on cell growth and induction of cell death. We found, similar to PTEN, overexpression of PTEN-Long in 786-0 cells inhibited cell proliferation and this depends on its lipid phosphatase activity as PTEN-LongG302R showed no effect (Fig. 3A).

Bottom Line: We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt).When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage.Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Institute of Urology, Zhifu, Yantai, Shandong, 264000, People's Republic of China.

ABSTRACT
PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.

Show MeSH
Related in: MedlinePlus