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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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PTEN-Long inhibits the proliferation of 786-0 cells in xenograft mouse model.A, 786-0 cells engrafted nude mice were treated with 5 mg/kg of PTEN or PTEN-Long for 6 days. PTEN-Long but not PTEN inhibited tumor growth. B, Graph of tumor diameters as measured by calipers and treated with either PTEN or PTEN-Long at 5 mg/kg for different time periods. n = 6; bars represent the means ± SD.
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pone-0114250-g007: PTEN-Long inhibits the proliferation of 786-0 cells in xenograft mouse model.A, 786-0 cells engrafted nude mice were treated with 5 mg/kg of PTEN or PTEN-Long for 6 days. PTEN-Long but not PTEN inhibited tumor growth. B, Graph of tumor diameters as measured by calipers and treated with either PTEN or PTEN-Long at 5 mg/kg for different time periods. n = 6; bars represent the means ± SD.

Mentions: We further explored the effect of PTEN-Long on proliferation of 786-0 cells in mouse xenograft model. We engraft 786-0 cells subcutaneously into athymic nude mice and waited until their tumor growth reached ∼0.5 cm of diameter. Mice carrying tumors were randomly divided into two groups and were injected intraperitoneally with PTEN or PTEN-Long at 5 mg/kg on daily basis. We found treatment with PTEN-Long caused tumor regression after 4 days (Fig. 7A and 7B). Taken together, these results indicated PTEN-Long protein is a potential protein drug against ccRCC.


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)

PTEN-Long inhibits the proliferation of 786-0 cells in xenograft mouse model.A, 786-0 cells engrafted nude mice were treated with 5 mg/kg of PTEN or PTEN-Long for 6 days. PTEN-Long but not PTEN inhibited tumor growth. B, Graph of tumor diameters as measured by calipers and treated with either PTEN or PTEN-Long at 5 mg/kg for different time periods. n = 6; bars represent the means ± SD.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114250-g007: PTEN-Long inhibits the proliferation of 786-0 cells in xenograft mouse model.A, 786-0 cells engrafted nude mice were treated with 5 mg/kg of PTEN or PTEN-Long for 6 days. PTEN-Long but not PTEN inhibited tumor growth. B, Graph of tumor diameters as measured by calipers and treated with either PTEN or PTEN-Long at 5 mg/kg for different time periods. n = 6; bars represent the means ± SD.
Mentions: We further explored the effect of PTEN-Long on proliferation of 786-0 cells in mouse xenograft model. We engraft 786-0 cells subcutaneously into athymic nude mice and waited until their tumor growth reached ∼0.5 cm of diameter. Mice carrying tumors were randomly divided into two groups and were injected intraperitoneally with PTEN or PTEN-Long at 5 mg/kg on daily basis. We found treatment with PTEN-Long caused tumor regression after 4 days (Fig. 7A and 7B). Taken together, these results indicated PTEN-Long protein is a potential protein drug against ccRCC.

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