[Obesity as a risk factor for prostate cancer: role for adipocytokines and involvement of tyrosine kinase pathway].
OBJECTIVE
Obesity is considered to be a risk factor for prostate cancer. Mitogenic actions of leptin, an adipocyte-derived hormone in a variety of cancer cell types have been identified. We have investigated the proliferative effects of leptin on human prostate cancer cells and assessed the role of tyrosine kinase signalling in mediating these actions.


METHODS
Two human androgen-resistant prostate cancer cell lines and one androgen-sensitive human prostate adenocarcinoma cell line were treated with leptin (5-100 ng / mL) for up to 48 hours. Under serum-free conditions, cell proliferation was measured using an enzyme-linked colorimetric assay. Furthermore, phosphorylation of a downstream component of MAPK (ERK1 / 2) was detected by Western blotting and a specific inhibitor of MAPK (PD98059; 40 microM) was used to evaluate the role of this signalling pathway.


RESULTS
Leptin dose-dependently increased the cell number in both androgen-resistant cell lines after 24 h and 48 h of incubation (percent of control: DU145 = 194.6 +/- 5.9 %, PC-3 = 177.9 +/- 6.8 %; 100 ng / mL leptin; 48 h; p < 0.001). Conversely, leptin's proliferative effect on the androgen-sensitive cell line was less pronounced (percent of control: LNCaP = 112.3 +/- 6.1 %; 100 ng / mL leptin; 48 h). Leptin also caused dose-dependent ERK1 / 2 phosphorylation in both androgen-resistant cell lines. In addition, pre-treatment with PD98059 inhibited these responses and attenuated leptin's mitogenic action.


CONCLUSIONS
Data from this in vitro study suggest an association between obesity-associated hyperleptinemia and an increased risk for prostate cancer. Further investigations are necessary to clarify whether these data have clinical relevance regarding the use as a prognostic marker for predicting the timing of the occurrence of androgen resistency.
Hoda
M R
MR
Universitätsklinik und Poliklinik für Urologie und Nierentransplantationszentrum, Medizinische Fakultät der MLU Halle / Wittenberg. rhoda@ucsd.edu
Hamza
A
A
Fischer
K
K
Wagner
S
S
Schneider
J
J
Heynemann
H
H
Fornara
P
P
D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D054392:Adipokines / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000502:physiology; D048370:MAP Kinase Kinase 2 / Q000502:physiology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology / Q000503:physiopathology*; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*
D054392:Adipokines; D020738:Leptin; D011505:Protein-Tyrosine Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2