In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

Cell Communication and Signaling

Ines Breuksch¹  Heide-Katharina Bauer¹  Walburgis Brenner¹  Annette Hasenburg¹  Dirk Prawitt²  Thorsten Enklaar²  Jonas Welter³  Sebastian Frees³  Joachim W. Thüroff³ 

[1] Department of Gynecology, Johannes Gutenberg University Medical Center;Department of Pediatrics, Johannes Gutenberg University Medical Center;Department of Urology, Johannes Gutenberg University Medical Center;

关键词: PTEN;    Renal cell carcinoma;    Splice variant;    PTEN-Δ;    Tumor progression;    Metastasis;   

DOI  :  10.1186/s12964-018-0247-9

来源: DOAJ

【 摘 要 】

Abstract Background Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression. Methods In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro. Results Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown. Conclusions We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.

【 授权许可】

Unknown