The role of the cellular retinoic acid binding protein type II (CRABPII) in the retinoic acid (RA) signaling pathway is poorly understood. Northern blot analysis of 12 breast cell lines showed that CRABPII mRNA content correlated with growth inhibition by RA, suggesting that this binding protein enhances cellular response to RA. Ectopic CRABPII expression supported dose-dependent growth inhibition by RA in SC115-resistant but not MDA-MB-231-resistant cells, indicating that CRABPII is sufficient to rescue RA antiproliferation in a permissive background. In both cell lines, ectopic binding protein enhanced gene activation by RA. Thus, induction of tissue transglutaminase by all-trans-RA and, surprisingly, 9-cis-RA was enhanced 5-fold over and above the level of induction in control cells (SC115), and activation of a RA response element reporter was enhanced 3-fold (MDA-MB-231). A 5-fold enhancement of RA induction of RA receptor beta expression as a result of ectopic binding protein expression was also demonstrated (SC115). These findings indicate that CRABPII is a positive regulator of RA signaling in breast cells.

1994-01-01·Journal of Nippon Medical School

マウス前立腺癌モデルに対するホルモン療法およびインターロイキン２，活性化マクロファージ局所療法の効果に関する実験的研究

Article

作者: Ikeda, K

In order to establish a more effective and safer therapy for androgen-dependent prostate cancer, to be used in addition to hormonal therapy, the anti-tumor effects of intralesionally administered macrophages activated with recombinant interferon-gamma (INF-gamma), alone or in combination with recombinant interleukin-2 (IL-2) were studied in mouse prostate cancer models. Firstly, in terms of cellular adoptive immunotherapy, phagocytosis against Latex bead and cytotoxicity against Shionogi 115 cancer cell line (SC115) of macrophages activated with INF-gamma for 24 hour were investigated. One ml of 0.25% glycogen solution was intraperitoneally administered to male DS mice. Three days later, fluid was aspirated from the abdominal cavity and macrophages were separated for use in this experiment. Phagocytosis INF-gamma-dose-dependently increased and macrophages activated with 100 U/ml INF-gamma phagocytosed 78.3 +/- 4.5% (mean +/- SD) Latex bead. Cytotoxicity (modified MTT assay) of SC 115 by macrophages activated with 100 U/ml INF-gamma increased remarkably in comparison with non-activated macrophages and there was a significant increase in the effector-to-target-cell ratio to 40 in the activated group 77 +/- 4.3% (mean +/- SD) relative to 50 +/- 6.3% (mean +/- SD) in the non-activated group. Based on these in vitro findings, hormonal therapy and adoptive local immunotherapy, alone or together, were studied in mouse prostate cancer models. The prostate cancer model was prepared through the subcutaneous transplantation of SC115 in male DS mice and the treatments were initiated after tumors were palpable. The therapy protocols were as follows: Group I control and Group II received 20 mg/kg/day diethylstilbestrol diphosphate (DES-P) subcutaneously for 10 days, Group III received DES-P in combination with ten thousand units of IL-2 administered five times intralesionally, Group IV received DES-P in combination with 2 x 10(6) macrophages activated with 100 U/ml INF-gamma administered three times intralesionally, Group V received DES-P and IL-2 in combination with activated macrophages. The therapeutic efficiencies were evaluated by calculating the tumor volume and survival time. The results of the tumor volume on the 40th day post tumor transplantation were as follows (mean +/- SD): Group I 7,049 +/- 1,477 mm3, Group II 4,495 +/- 654 mm3, Group III 2,050 +/- 724 mm3, Group IV 2,782 +/- 970 mm3, Group V 1,555 +/- 514 mm3. The therapeutic groups showed significant tumor reduction relative to the control. Furthermore, intralesionally IL-2, the activated macrophages injected groups, alone or together, were more effective relative to the group receiving only DES-P.(ABSTRACT TRUNCATED AT 400 WORDS)

1992-07-01·The Journal of Steroid Biochemistry and Molecular Biology2区 · 生物学

Loss of androgen dependency with preservation of functional androgen receptors in androgen-dependent mouse tumor (Shionogi carcinoma 115)

2区 · 生物学

Article

作者: Yoshio Watabe ; Naohide Sato ; Hiroshi Shirasawa ; Bunsiti Simizu ; Jun Shimazaki ; Yuzo Furuya

Shionogi Carcinoma 115 (SC 115) is an androgen-dependent mouse tumor. Chiba Subline 2 (CS 2) is an androgen-independent subline derived from SC 115. CS 2 contains androgen receptors (AR), but is refractory to androgen and does not exhibit androgen-related responses which are observed in SC 115. In the present study the structure and function of AR in SC 115 and CS 2 are examined using cloned cells. There were no gross rearrangements or deletions in the AR genes of these cell lines when compared by Southern blot analysis with the AR gene in the mouse seminal vesicle. SC 115 and CS 2 expressed AR mRNA of normal size. When the cDNA containing DNA- and androgen-binding domains of the AR genes of both cell lines were amplified by polymerase chain reaction, no mutations were found in these regions. SC 115 and CS 2 were transfected with a plasmid containing a long terminal repeat of mouse mammary tumor virus linked to the chloramphenicol acetyltransferase (CAT) gene. Androgen stimulation of these transfectants resulted in equal elevation of CAT activity. These results indicated that the androgen-independent CS 2 contained functionally normal AR which were identical to those in the androgen-dependent parent tumor.

100 项与 SC-115 相关的药物交易

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