Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression.
OBJECTIVE
Id proteins are dominant-negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of Id-1 and Id-2 proteins as molecular makers for prostate cancer progression.


METHODS
Using the technique of immunohistochemistry, we determined Id-1 and Id-2 expression in a panel of 67 human prostate biopsies. We also manipulated Id-1 and Id-2 expression in LNCaP and PC3 prostate cancer cell lines and determined the effects on invasion in vitro, matrix metalloproteinase secretion, and proliferation.


RESULTS
Both Id-1 and Id-2 proteins were up-regulated during human prostate cancer progression in vivo and were overexpressed in highly aggressive prostate cancer cells. In vitro, constitutive expression of Id-1, and to a lesser extent Id-2, converted nonaggressive LNCaP prostate cancer cells into more proliferative and invasive cells and increased their secretion of matrix metalloproteinases. Conversely, the down-regulation of Id-2 expression in highly metastatic PC3 cells reduced their growth potential and invasiveness.


CONCLUSIONS
We propose that both Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer.
Coppe
Jean-Philippe
JP
California Pacific Medical Center, Cancer Research Institute, San Francisco, California 94115, USA.
Itahana
Yoko
Y
Moore
Dan H
DH
Bennington
James L
JL
Desprez
Pierre-Yves
PY
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D018450:Disease Progression; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497450:ID2 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors