Limits...
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.

Show MeSH

Related in: MedlinePlus

Protein expression of PTEN-Long was significantly reduced or lost in ccRCC.A, Western blot analysis of PTEN, PTEN-Long, and pAkt. Represented are 6 pairs of clear cell renal cell carcinomas and their corresponding normal renal tissues. In clear cell renal cell carcinomas the PTEN-Long expression was either negative or very weak, compared to normal renal tissue. N, normal renal tissue; T, tumor tissue. B, The ratio of PTEN, PTEN-Long, Akt, and pAkt to Actin in 45 samples. The PTEN-Long expression in ccRCC was reduced significantly in comparison with the corresponding normal renal tissue. Note that tumor samples with undetectable PTEN-Long and PTEN were excluded from quantification.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4340966&req=5

pone-0114250-g001: Protein expression of PTEN-Long was significantly reduced or lost in ccRCC.A, Western blot analysis of PTEN, PTEN-Long, and pAkt. Represented are 6 pairs of clear cell renal cell carcinomas and their corresponding normal renal tissues. In clear cell renal cell carcinomas the PTEN-Long expression was either negative or very weak, compared to normal renal tissue. N, normal renal tissue; T, tumor tissue. B, The ratio of PTEN, PTEN-Long, Akt, and pAkt to Actin in 45 samples. The PTEN-Long expression in ccRCC was reduced significantly in comparison with the corresponding normal renal tissue. Note that tumor samples with undetectable PTEN-Long and PTEN were excluded from quantification.

Mentions: To study if PTEN-Long plays a role in ccRCC, we examined protein expression of PTEN-Long in 50 ccRCC and the corresponding normal renal tissue of the same patients using Western blotting analysis. PTEN-Long was expressed in all investigated normal renal tissue specimens. However, PTEN-Long expression in ccRCCs was markedly reduced in comparison with normal tissue, as evidenced by Western blotting analysis (Fig. 1A). In 35% of all ccRCCs studied, PTEN-Long expression was undetectable, probably due to genomic loss of PTEN or truncation mutations that destabilize PTEN or PTEN-Long proteins. Akt is well known to be activated by phosphorylation at Ser 473. We therefore examined the Akt activation status in ccRCC by western blotting using antibody against phosphorylated Akt (pAkt), which recognizes only phosphorylated Akt at Ser 473. The expression of total Akt protein in ccRCC and the corresponding kidney tissue were at similar levels. In contrast, the levels of pAkt were observed to increase significantly in ccRCC, in comparison with levels of pAkt in the corresponding normal kidney tissue (Fig. 1A). Therefore, the pAkt level inversely correlated with the PTEN-Long level.


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)

Protein expression of PTEN-Long was significantly reduced or lost in ccRCC.A, Western blot analysis of PTEN, PTEN-Long, and pAkt. Represented are 6 pairs of clear cell renal cell carcinomas and their corresponding normal renal tissues. In clear cell renal cell carcinomas the PTEN-Long expression was either negative or very weak, compared to normal renal tissue. N, normal renal tissue; T, tumor tissue. B, The ratio of PTEN, PTEN-Long, Akt, and pAkt to Actin in 45 samples. The PTEN-Long expression in ccRCC was reduced significantly in comparison with the corresponding normal renal tissue. Note that tumor samples with undetectable PTEN-Long and PTEN were excluded from quantification.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114250-g001: Protein expression of PTEN-Long was significantly reduced or lost in ccRCC.A, Western blot analysis of PTEN, PTEN-Long, and pAkt. Represented are 6 pairs of clear cell renal cell carcinomas and their corresponding normal renal tissues. In clear cell renal cell carcinomas the PTEN-Long expression was either negative or very weak, compared to normal renal tissue. N, normal renal tissue; T, tumor tissue. B, The ratio of PTEN, PTEN-Long, Akt, and pAkt to Actin in 45 samples. The PTEN-Long expression in ccRCC was reduced significantly in comparison with the corresponding normal renal tissue. Note that tumor samples with undetectable PTEN-Long and PTEN were excluded from quantification.
Mentions: To study if PTEN-Long plays a role in ccRCC, we examined protein expression of PTEN-Long in 50 ccRCC and the corresponding normal renal tissue of the same patients using Western blotting analysis. PTEN-Long was expressed in all investigated normal renal tissue specimens. However, PTEN-Long expression in ccRCCs was markedly reduced in comparison with normal tissue, as evidenced by Western blotting analysis (Fig. 1A). In 35% of all ccRCCs studied, PTEN-Long expression was undetectable, probably due to genomic loss of PTEN or truncation mutations that destabilize PTEN or PTEN-Long proteins. Akt is well known to be activated by phosphorylation at Ser 473. We therefore examined the Akt activation status in ccRCC by western blotting using antibody against phosphorylated Akt (pAkt), which recognizes only phosphorylated Akt at Ser 473. The expression of total Akt protein in ccRCC and the corresponding kidney tissue were at similar levels. In contrast, the levels of pAkt were observed to increase significantly in ccRCC, in comparison with levels of pAkt in the corresponding normal kidney tissue (Fig. 1A). Therefore, the pAkt level inversely correlated with the PTEN-Long level.

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