The helix-loop-helix Id-1 inhibits PSA expression in prostate cancer cells.
The inhibitor of basic helix-loop-helix transcription factors, Id-1, is an important gene whose expression increases during prostate cancer progression and that upregulates proliferation, migration and invasion. We used microarray analysis to identify the downstream genes whose transcriptional expression is modulated by Id-1 protein. We compared gene expression in control LNCaP cells and Id-1-transduced LNCaP cells, which become significantly more aggressive after Id-1 overexpression, thus mimicking the high levels of Id-1 detected in metastatic cell lines. We used the Affy HTA U133A Expression Arrays with 45,000 probe sets representing more than 39,000 transcripts. We found that one of the most significantly downregulated genes on Id-1 expression was kallikrein 3 [also called prostate specific antigen (PSA)], the most commonly used biomarker of prostate cancer. Here, we show that the reduction in PSA mRNA and protein expression associated with high-grade prostate cancers, which generally express high levels of Id-1, could be the consequence of Id-1 overexpression.
Zielinski
Anne J
AJ
California Pacific Medical Center, Cancer Research Institute, San Francisco, CA 94107, USA.
Fong
Sylvia
S
Allison
Juanita
J
Kawahara
Misako
M
Coppe
Jean-Philippe
JP
Feiler
Heidi
H
Lee
Nancy M
NM
Desprez
Pierre-Yves
PY
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs / Q000187:drug effects; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000187:drug effects / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D034741:RNA, Small Interfering; D017430:Prostate-Specific Antigen