High mobility group protein AT-hook 1 (HMGA1) is associated with the development of androgen independence in prostate cancer cells.
BACKGROUND
We previously reported that the level of high mobility group protein AT-hook 1 (HMGA1) is low in androgen-dependent prostate cancer (PCa) cells (LNCaP), but is high in androgen-independent PCa cells (DU145 and PC-3) and that HMGA1 is a strong candidate gene playing a potential role in the progression of PCa. These findings have prompted us to evaluate the effect of HMGA1 on developing androgen independency, which is associated with the progression of PCa.


METHODS
Expression of HMGA1 in PCa cells and mouse tissues was examined by Western blot. In order to examine the effect of HMGA1 on cell growth under androgen-deprived condition, we transfected HMGA1 into LNCaP cells, and siRNA into both DU145 and PC-3 cells, respectively.


RESULTS
Androgen-deprivation induced an increase in the level of HMGA1 in LNCaP cells in vitro and in vivo, but did not in normal prostate tissue. Overexpression of HMGA1 maintained the cell growth of LNCaP under androgen-deprived condition. Furthermore, knockdown of HMGA1 suppressed the cell growth of DU145 and PC-3.


CONCLUSIONS
These data suggest that elevated expression of HMGA1 is associated with the transition of PCa cells from androgen-sensitive to androgen-independent growth and plays a role in the cell growth of androgen-independent PCa cells.
Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ichiro
I
Takeuchi
Natsuki
N
Takaha
Terukazu
T
Nakamura
Fumiya
F
Hongo
Kazuya
K
Mikami
Kazumi
K
Kamoi
Koji
K
Okihara
Akihiro
A
Kawauchi
Tsuneharu
T
Miki
D000728:Androgens / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D025741:HMGA1a Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D000728:Androgens; D025741:HMGA1a Protein