Differential regulation of IGFBP-3 by the androgen receptor in the lineage-related androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer models.
BACKGROUND
Despite evidence implicating insulin-like growth factor binding protein-3 (IGFBP-3) as a growth inhibitor of prostate cancer (CaP), little is known about changes in its regulation and function during progression to androgen independence.


METHODS
The expression levels of IGFBP-3 were determined by cDNA microarray analysis and tissue microarrays (TMAs) after androgen ablations. LNCaP (LN-BP3) and C4-2 (C4-2-BP3) sublines were used to compare the apoptotic effects of IGFBP-3 in LNCaP (androgen-dependent) and C4-2 (androgen-independent) cells.


RESULTS
After androgen deprivation, IGFBP-3 mRNA levels increased more in C4-2 compared to LNCaP cells. Androgens suppressed IGFBP-3 levels in a dose-dependent manner in LNCaP and C4-2 cell. IGFBP-3 expression was increased after NHT in human CaP tissues. Apoptotic rates increased in LN-BP3, but not C4-2-BP3 cells, following doxycycline-mediated IGFBP-3 induction.


CONCLUSIONS
C4-2 cell survival in an androgen-depleted environment may be facilitated through differential resistance to the apoptotic effects elicited by IGFBP-3.
Kojima
Satoko
S
The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Mulholland
David J
DJ
Ettinger
Susan
S
Fazli
Ladan
L
Nelson
Colleen C
CC
Gleave
Martin E
ME
D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002470:Cell Survival; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000502:physiology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011944:Receptors, Androgen / Q000502:physiology*
D000728:Androgens; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011944:Receptors, Androgen; D004318:Doxycycline