Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression.
BACKGROUND
Proteins which regulate normal development may promote tumorigenesis, tumor progression, or metastasis through dysregulation of these functions. We postulate that proteins, which regulate prostate growth also promote prostate cancer (PCa) progression.


METHODS
Two Dimensional Gel Electrophoresis was utilized to compare patterns of protein expression in 12T-7f prostates (LPB-Tag mouse model for PCa) during tumor development and progression with those of normal developing and adult wild type CD-1 prostates. Stathmin expression and phosphorylation patterns were analyzed in mouse and human PCa cell lines as well as in human PCa tissue arrays.


RESULTS
Stathmin was identified by two-dimensional gel electrophoresis and mass spectrometry. Stathmin levels increase early during normal mouse prostate development and again during prostate tumor development and progression. In human prostate adenocarcinoma, stathmin increases in Gleason pattern 5. Further, stathmin is differentially phosphorylated in androgen-dependent LNCaP cells compared to androgen-independent PC-3 and DU145 cells. This differential phosphorylation is modulated by androgen and anti-androgen treatment.


CONCLUSIONS
Stathmin expression is highest when the prostate is undergoing morphogenesis or tumorigenesis and these processes may be regulated through differential phosphorylation. Furthermore, modulation of stathmin phosphorylation may correlate with the development of androgen-independent PCa.
Ghosh
Ritwik
R
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA.
Gu
Guangyu
G
Tillman
Erin
E
Yuan
Jialing
J
Wang
Yongqing
Y
Fazli
Ladan
L
Rennie
Paul S
PS
Kasper
Susan
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000728:Androgens / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D010766:Phosphorylation; D011467:Prostate / Q000254:growth & development / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D000728:Androgens; D050777:Stathmin