Kogan I, Ballinger J R, Redshaw R, Diamandis E P, Melegos D N, Kuba R M, Rauth A M
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Breast Cancer Res Treat. 1998 Mar;48(1):73-80. doi: 10.1023/a:1005947024666.
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.
先前的研究表明，超过30%的人类乳腺肿瘤胞质溶胶中存在前列腺特异性抗原（PSA）。生存分析显示，产生PSA的肿瘤患者复发风险降低，这表明PSA是一大类乳腺癌患者独立的有利预后标志物。本研究建立了一种体内模型，用于诱导在严重联合免疫缺陷（SCID）小鼠体内异种移植生长的人类乳腺肿瘤产生PSA。将人乳腺癌细胞系T47D接种于雌性小鼠的肌肉中。当肿瘤和腿部直径达到10毫米时，每天用炔诺孕酮刺激小鼠5天或7天以产生PSA，并在第8天处死。前列腺癌细胞系LNCaP接种于雄性小鼠体内，作为PSA产生的阳性对照。处死T47D和LNCaP小鼠后，采用高灵敏度免疫荧光测定法分析肿瘤、肌肉、肝脏和肾脏胞质溶胶中的PSA浓度。与对照小鼠的肿瘤相比，炔诺孕酮刺激的T47D小鼠肿瘤中PSA含量显著更高。然而，刺激小鼠肿瘤中的PSA水平显著低于LNCaP异种移植物中的水平。在炔诺孕酮刺激的或对照T47D异种移植物的血液和正常组织中，未检测到高于背景水平的PSA。该小鼠模型将成为研究和筛选针对肿瘤中PSA浓度显著的乳腺癌患者亚组的新疗法的有价值工具。
