Dataset Information

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

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-?. We analyzed the impact of PTEN-? in RCC progression.

Methods

In specimens of RCC patients the expression of PTEN-? 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-? or PTEN transcript. In Caki-1 cells that highly express PTEN-?, 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-? expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-? expression correlated with the PTEN expression. PTEN-? as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-?, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-? and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-?. 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-? acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-? in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.

SUBMITTER: Breuksch I

PROVIDER: S-EPMC6025732 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Breuksch Ines I Welter Jonas J Bauer Heide-Katharina HK Enklaar Thorsten T Frees Sebastian S Thüroff Joachim W JW Hasenburg Annette A Prawitt Dirk D Brenner Walburgis W

Cell communication and signaling : CCS 20180628 1

<h4>Background</h4>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.<h4>Methods</h4>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 trans ...[more]

PMID: 29954386

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