6 research outputs found
In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself
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
The role of extracellular calcium in bone metastasis
This review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis
Additional file 2: of In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself
Figure S2. Influence of PTEN-∆ and PTEN on proliferation. Proliferation was determined by BrdU incorporation. Differences are shown as percentage of the transfection control cells (pcDNA3 transfected cells). (PDF 90 kb
Additional file 3: of In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself
Figure S3. Human phospho-kinase array (Roche) of transfected 786-O and A498 cells. Protein extracts were obtained from PTEN-Δ and PTEN transfected cells and analyzed concerning the phosphorylation status of 46 intracellular signaling kinases. The activity of the kinases AKT, JNK and p38 are highlighted with red boxes. (PDF 111 kb
Additional file 1: of In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself
Figure S1. Western blot of A498 and 786-O cells. Protein extracts of A498 and 786-O cells were analyzed concerning the expression value of PTEN. (PDF 89 kb