Prostate-specific antigen induction by a steroid hormone in T47D cells growing in SCID mice.
Previous studies revealed that prostate-specific antigen (PSA) is present in > 30% of human breast tumor cytosols. Survival analysis showed that patients with PSA-producing tumors have a reduced risk for relapse, suggesting PSA to be an independent favorable prognostic marker for a large subset of breast cancer patients. The present investigation established an in vivo model for the induction of PSA in human breast cancer tumors growing as xenografts in severe combined immunodeficient (SCID) mice. The human mammary cancer cell-line T47D was grown i.m. in female mice. When the tumor and leg diameter reached 10 mm, the mice were stimulated daily with norgestrel for either 5 or 7 days to produce PSA, and sacrificed on day 8. The prostate cancer cell-line LNCaP was grown in male mice and functioned as a positive control for PSA production. After T47D and LNCaP mice were sacrificed, a highly sensitive immunofluorometric assay was used to analyze the PSA concentration in the tumor, muscle, liver, and kidney cytosols. Norgestrel-stimulated T47D mice showed significantly more PSA in the tumors compared to tumors of the control mice. However, PSA levels in tumors of the stimulated mice were significantly lower than those in the LNCaP xenografts. No PSA levels above background were present in the blood and normal tissue of the norgestrel-stimulated or control T47D xenografts. This mouse model will be a valuable tool for investigating and screening new therapies for a subgroup of breast cancer patients who have significant PSA concentrations in their tumors.
Kogan
I
I
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Ballinger
J R
JR
Redshaw
R
R
Diamandis
E P
EP
Melegos
D N
DN
Kuba
R M
RM
Rauth
A M
AM
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009644:Norgestrel / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured
D045167:Progesterone Congeners; D009644:Norgestrel; D017430:Prostate-Specific Antigen