In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 20 ( 2000-09-26), p. 10990-10995
Abstract:
Peroxisome proliferator-activated receptor γ (PPARγ) is a
nuclear hormone receptor that plays a key role in the differentiation of adipocytes. Activation of this receptor in liposarcomas and breast
and colon cancer cells also induces cell growth inhibition and differentiation. In the present study, we show that PPARγ is
expressed in human prostate adenocarcinomas and cell lines derived from these tumors. Activation of this receptor with specific ligands exerts
an inhibitory effect on the growth of prostate cancer cell lines. Further, we show that prostate cancer and cell lines do not have
intragenic mutations in the PPARγ gene, although 40% of the informative tumors have hemizygous deletions of this gene. Based on our
preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPARγ ligand used
for the treatment of type 2 diabetes. Forty-one men with histologically confirmed prostate cancer and no symptomatic metastatic disease were
treated orally with troglitazone. An unexpectedly high incidence of prolonged stabilization of prostate-specific antigen was seen in
patients treated with troglitazone. In addition, one patient had a dramatic decrease in serum prostate-specific antigen to nearly
undetectable levels. These data suggest that PPARγ may serve as a biological modifier in human prostate cancer and its therapeutic
potential in this disease should be further investigated.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.180329197
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
