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The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Hoda MR, Theil G, Mohammed N, Fischer K, Fornara P - J Oncol (2012)

Bottom Line: Background.Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used.Results.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Urology and Kidney Transplantation Centre, University Medical School of Halle/Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle, Saale, Germany.

ABSTRACT
Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

No MeSH data available.


Related in: MedlinePlus

Leptin activates ERK1/2 isoforms of MAPK signaling pathway in a dose-dependent manner in androgen-resistant prostate cancer cell lines (DU145 and PC-3). Three different human prostate cancer cell lines were cultured in serum-free media for 24 hrs followed by exposure to recombinant human leptin for 1 hour. Cellular extracts were fractioned onto 12% SDS-Page and Western immunoblotting performed with a rabbit polyclonal anti-phospho-p44/42 MAPK as described in Section 2. The findings are from a single experiment representative of at least 3 similar experiments.
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fig2: Leptin activates ERK1/2 isoforms of MAPK signaling pathway in a dose-dependent manner in androgen-resistant prostate cancer cell lines (DU145 and PC-3). Three different human prostate cancer cell lines were cultured in serum-free media for 24 hrs followed by exposure to recombinant human leptin for 1 hour. Cellular extracts were fractioned onto 12% SDS-Page and Western immunoblotting performed with a rabbit polyclonal anti-phospho-p44/42 MAPK as described in Section 2. The findings are from a single experiment representative of at least 3 similar experiments.

Mentions: A common intracellular pathway that has been shown to be recruited by leptin receptors is the mitogen-activated protein kinase (MAPK) cascade [17, 23, 24]. To evaluate if leptin's mitogenic action in androgen-resistant prostate cancer cells is linked to proliferative signaling through activation of the MAPK signaling pathway, DU145, PC-3, and LNCaP cells were treated with leptin and phosphorylation of p42/44 MAPK (ERK1/2), a downstream component of MAPK pathway was measured by Western blotting using phosphospecific antibodies. As would be expected from proliferation assay data, leptin treatment evoked ERK phosphorylation in both androgen-resistant cell lines in a dose-dependent manner (Figures 2(a) and 2(b)). In LNCaP cells, however, leptin also evoked activation of ERK phosphorylation, but to a comparably lesser extent (data not shown).


The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Hoda MR, Theil G, Mohammed N, Fischer K, Fornara P - J Oncol (2012)

Leptin activates ERK1/2 isoforms of MAPK signaling pathway in a dose-dependent manner in androgen-resistant prostate cancer cell lines (DU145 and PC-3). Three different human prostate cancer cell lines were cultured in serum-free media for 24 hrs followed by exposure to recombinant human leptin for 1 hour. Cellular extracts were fractioned onto 12% SDS-Page and Western immunoblotting performed with a rabbit polyclonal anti-phospho-p44/42 MAPK as described in Section 2. The findings are from a single experiment representative of at least 3 similar experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368429&req=5

fig2: Leptin activates ERK1/2 isoforms of MAPK signaling pathway in a dose-dependent manner in androgen-resistant prostate cancer cell lines (DU145 and PC-3). Three different human prostate cancer cell lines were cultured in serum-free media for 24 hrs followed by exposure to recombinant human leptin for 1 hour. Cellular extracts were fractioned onto 12% SDS-Page and Western immunoblotting performed with a rabbit polyclonal anti-phospho-p44/42 MAPK as described in Section 2. The findings are from a single experiment representative of at least 3 similar experiments.
Mentions: A common intracellular pathway that has been shown to be recruited by leptin receptors is the mitogen-activated protein kinase (MAPK) cascade [17, 23, 24]. To evaluate if leptin's mitogenic action in androgen-resistant prostate cancer cells is linked to proliferative signaling through activation of the MAPK signaling pathway, DU145, PC-3, and LNCaP cells were treated with leptin and phosphorylation of p42/44 MAPK (ERK1/2), a downstream component of MAPK pathway was measured by Western blotting using phosphospecific antibodies. As would be expected from proliferation assay data, leptin treatment evoked ERK phosphorylation in both androgen-resistant cell lines in a dose-dependent manner (Figures 2(a) and 2(b)). In LNCaP cells, however, leptin also evoked activation of ERK phosphorylation, but to a comparably lesser extent (data not shown).

Bottom Line: Background.Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used.Results.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Urology and Kidney Transplantation Centre, University Medical School of Halle/Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle, Saale, Germany.

ABSTRACT
Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

No MeSH data available.


Related in: MedlinePlus