Landström M, Eklöv S, Colosetti P, Nilsson S, Damber J E, Bergh A, Funa K
Department of Pathology, University of Umeà, Sweden.
Int J Cancer. 1996 Aug 7;67(4):573-9. doi: 10.1002/(SICI)1097-0215(19960807)67:4<573::AID-IJC17>3.0.CO;2-8.
Rats transplanted with the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma were castrated and treated with either estrogen or vehicle alone for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks. In these tumors the expression of TGF-beta 1, TGF-beta type-I and type-II receptors (TGF-beta RI, TGF-beta RII) was examined by immunohistochemistry. Apoptotic cells were identified by in situ nick and labelling (TUNEL). Tumor growth was retarded by castration and even more by additive estrogen treatment. The epithelium of the untreated tumors stained weakly for TGF-beta 1 and TGF-beta RI, but TGF-beta RII was not detected. Castration induced moderate TGF-beta 1 immunoreactivity in a major part of the glandular epithelium after 24 hr. After 12 hr already, castration plus estrogen resulted in an intense staining for TGF-beta 1 in the basal epithelial cells, some of which also showed an apoptotic appearance. The percentage of cells having stained positive for TGF-beta 1 was significantly higher in the estrogen-treated groups than in the castrated group after 12 hr, and its elevated TGF-beta 1 level remained at 6 weeks. Notably, the increased immunoexpression of TGF-beta 1 occurred before the onset of induction of apoptosis. In parallel with the upregulation of TGF-beta 1 after castration, the expression of its receptors. TGF-beta RI and RII, was induced and was further enhanced by the additive estrogen treatment. The number of intensely stained TGF-beta 1 tumor cells showed a strong correlation with the number of apoptotic tumor cells identified by TUNEL in the whole material. Furthermore, TGF-beta 1 immunoreactivity co-localized with the presence of apoptotic cells in the estrogen-treated tumors at 6 weeks after castration.
将雄激素敏感的邓宁R3327 PAP前列腺腺癌移植到大鼠体内，对其进行去势，并分别用雌激素或单独的赋形剂短期（4小时、12小时、24小时）及6周进行处理。通过免疫组织化学检测这些肿瘤中转化生长因子β1（TGF-β1）、转化生长因子βⅠ型和Ⅱ型受体（TGF-βRI、TGF-βRII）的表达。通过原位缺口标记法（TUNEL）鉴定凋亡细胞。去势可抑制肿瘤生长，而联合雌激素治疗的抑制作用更强。未经处理的肿瘤上皮细胞中，TGF-β1和TGF-βRI染色较弱，但未检测到TGF-βRII。去势24小时后，大部分腺上皮细胞出现中等程度的TGF-β1免疫反应性。去势加雌激素处理12小时后，基底上皮细胞中TGF-β1染色强烈，其中一些细胞也呈现凋亡外观。雌激素处理组在12小时后TGF-β1染色阳性的细胞百分比显著高于去势组，且其升高的TGF-β1水平在6周时仍维持不变。值得注意的是，TGF-β1免疫表达增加发生在凋亡诱导之前。与去势后TGF-β1上调同时，其受体TGF-βRI和RII的表达被诱导，且联合雌激素治疗使其进一步增强。在整个样本中，TGF-β1染色强烈的肿瘤细胞数量与TUNEL法鉴定的凋亡肿瘤细胞数量密切相关。此外，去势6周后，雌激素处理的肿瘤中TGF-β1免疫反应性与凋亡细胞的存在共定位。
