Purification of activins from androgen-independent Shionogi carcinoma cells demonstrates enhanced expression of activin betaB-subunit under androgen-depleted cell conditions in vitro and in vivo.
Here, we report characterization of growth factors secreted from androgen-independent mouse mammary Shionogi carcinoma cells. Previous isolation of fibroblast growth factor 8 (FGF8) from androgen-dependent Shionogi carcinoma SC-3 cells prompted us to characterize growth factors secreted from the androgen-independent cells. After several purification procedures, mitogens for NIH3T3 cells from the androgen-independent cells were identified as activins on the grounds that activin betaA- and betaB-subunits are detected in the active fractions by Western blotting and that the growth-promoting effects by the active fractions are specifically inhibited in the presence of follistatin. In addition, exogenous activins, but not inhibin, stimulated the growth of NIH3T3 cells in a dose-dependent manner. Interestingly, transcripts of activin betaB-subunit were predominantly found in the androgen-independent cells while its betaA-subunit was universally expressed in both androgen-dependent and -independent Shionogi carcinoma cells. In concordant with this in vitro finding, transcripts of activin betaB-subunit were enhanced in murine prostates after castration. Therefore, expression of activin betaB-subunit, but not its betaA-subunit, is likely to be related with androgen-depleted cell conditions in prostates, and possibly in androgen-related cancers.
Tanaka
A
A
Department of Pathology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi, Japan. atanaka@jichi.ac.jp
Hasegawa
Y
Y
Hakamata
Y
Y
Kamiakito
T
T
Kuriki
K
K
Yoshida
H
H
Fukayama
M
M
D016475:3T3 Cells; D028341:Activins; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004822:Epididymis / Q000378:metabolism; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000302:isolation & purification / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D066298:In Vitro Techniques; D028322:Inhibin-beta Subunits; D007265:Inhibins / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000503:physiopathology; D009919:Orchiectomy; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification; D011467:Prostate / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D000728:Androgens; C496457:Fgf8 protein, mouse; D010455:Peptides; D012333:RNA, Messenger; C044147:activin B; C103008:inhibin beta A subunit; D028341:Activins; D051524:Fibroblast Growth Factor 8; D007265:Inhibins; D005346:Fibroblast Growth Factors; D028322:Inhibin-beta Subunits