Selective activation of the fatty acid synthesis pathway in human prostate cancer.
A substantial subset of breast, colorectal, ovarian, endometrial and prostatic cancers displays markedly elevated expression of immunohistochemically detectable fatty acid synthase, a feature that has been associated with poor prognosis and that may be exploited in anti-neoplastic therapy. Here, using an RNA array hybridisation technique complemented by in situ hybridisation, we report that in prostate cancer fatty acid synthase expression is up-regulated at the mRNA level together with other enzymes of the same metabolic pathway. Contrary to the observations that in many cell systems (including androgen-stimulated LNCaP prostate cancer cells) fatty acid and cholesterol metabolism are co-ordinately regulated so as to supply balanced amounts of lipids for membrane biosynthesis, storage or secretion, no changes in the expression of genes involved in cholesterol synthesis were found. These findings point to selective activation of the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic gene expression in a subgroup of prostate cancers.
Swinnen
J V
JV
Laboratory for Experimental Medicine and Endocrinology, Gasthuisberg, Catholic University of Leuven, Belgium. Johan.Swinnen@med.kuleven.ac.be
Vanderhoydonc
F
F
Elgamal
A A
AA
Eelen
M
M
Vercaeren
I
I
Joniau
S
S
Van Poppel
H
H
Baert
L
L
Goossens
K
K
Heyns
W
W
Verhoeven
G
G
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000135:Acid Phosphatase / Q000235:genetics; D064429:Fatty Acid Synthases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D010455:Peptides / Q000235:genetics; D011467:Prostate / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
D010455:Peptides; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger; C043076:beta-microseminoprotein; D006903:Hydroxymethylglutaryl CoA Reductases; D064429:Fatty Acid Synthases; D000135:Acid Phosphatase; D000103:Acetyl-CoA Carboxylase