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Altered expression of genes regulating angiogenesis in experimental androgen-independent prostate cancer.

Artikel i vetenskaplig tidskrift
Författare Helene Gustavsson
Karin Jennbacken
Karin Welén
Jan-Erik Damber
Publicerad i Prostate
Volym 68
Nummer/häfte 2
Sidor 161-170
ISSN 1097-0045
Publiceringsår 2008
Publicerad vid Institutionen för kliniska vetenskaper
Sidor 161-170
Språk en
Länkar dx.doi.org/10.1002/pros.20672
Ämnesord ADAMTS1, hormone refractory, LNCaP-19, microarray, versican
Ämneskategorier Urologi och andrologi

Sammanfattning

BACKGROUND The aim of this study was to investigate how the expression of genes regulating angiogenesis is altered when prostate cancer cells progress into androgen-independency. METHODS A gene array specific for angiogenesis was used to compare the human prostate cancer cell line LNCaP (androgen-dependent) with its more angiogenic and tumorigenic subline LNCaP-19 (androgen-independent). Results were verified with real-time RT-PCR, and further investigations were focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in vitro as well as in subcutaneous tumors with real-time RT-PCR and Western blotting. Microvessel density (MVD), versican proteolysis and protein levels of TIMP-2 and TIMP-3, known as ADAMTS1 inhibitors, were also analyzed in tumor xenografts. RESULTS The gene array revealed decreased expression of ADAMTS1, ephrin-A5, fibronectin 1, and neuropilin 1 in LNCaP-19 compared to LNCaP, while expression of midkine and VEGF were increased. Further studies showed that mRNA and protein levels of ADAMTS1 were significantly lower in LNCaP-19 compared to LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated negatively with MVD, but no relation was found between ADAMTS1 and versican proteolysis. CONCLUSIONS Expression of several genes associated with angiogenesis was altered during transition into androgen-independency. Among these, a significant decrease was found for ADAMTS1, whose expression inversely correlated with MVD. Its role in progression of prostate cancer needs further investigation, but this inhibitor of angiogenesis could be an interesting candidate for future anti-angiogenic therapy.

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