Effects of testosterone and 17β‑estradiol on angiotensin‑induced changes in tyrosine kinase activity in the androgen‑independent human prostate cancer cell line, DU145

Domińska,Kamila; Kowalski,Antoni; Ochędalski,Tomasz; Rębas,Elżbieta

doi:10.3892/ijmm.2017.3149

Effects of testosterone and 17β‑estradiol on angiotensin‑induced changes in tyrosine kinase activity in the androgen‑independent human prostate cancer cell line, DU145

Authors:
- Kamila Domińska
- Antoni Kowalski
- Tomasz Ochędalski
- Elżbieta Rębas
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Affiliations: Department of Comparative Endocrinology, Medical University of Lodz, 92‑215 Lodz, Poland, Department of Molecular Neurochemistry, Medical University of Lodz, 92‑215 Lodz, Poland
Published online on: September 25, 2017 https://doi.org/10.3892/ijmm.2017.3149
Pages: 1573-1581

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Abstract

Angiotensin II (AngII), the main peptide of the renin‑angiotensin system (RAS), is involved in the proliferation of different types of cells, normal and pathological as well. The protein tyrosine kinases (PTKs) play an important role in the growth, differentiation and apoptosis of cells. AngII action depends on the hormonal milieu of the cell, and on sex steroid influence. Angiotensin 1‑7 (Ang1‑7), metabolite of AngII, shows opposite action to AngII in cells. The present study aimed to examine the influence of 17β‑estradiol and testosterone on AngII and Ang1‑7 action on PTK activity in androgen‑independent humane prostate cancer cell line DU145. Cell cultures of human prostate cancer DU145 cells were used as a source of PTKs. Cultures were exposed to different concentrations of AngII (5x10‑11 to 5x10‑9 M). The incubation with hormones lasted 15 min to limit the genomic effects of steroids. In the phosphorylation reaction, we used γ32P‑ATP as a donor of phosphate and a synthetic peptide, Poly(Glu, Tyr) (4:1), as a substrate. The specific activities of PTKs were defined as pmol of 32P incorporated into 1 mg of exogenous Poly(Glu, Tyr) per minute (pmol/mg/min). Our findings suggest that testosterone and 17β‑estradiol may change the effects of angiotensins in a rapid non‑genomic way, probably via membrane‑located receptors. The most significant change was caused by testosterone, whose effect was most significant on changes caused by Ang1‑7. AngII‑induced changes in phosphorylation appeared to be insensitive to the presence of testosterone, but were modified by 17β‑estradiol.

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