Dixon D, He H, Haseman J K
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Environ Health Perspect. 2000 Oct;108 Suppl 5:795-802. doi: 10.1289/ehp.00108s5795.
Immunolocalization of transforming growth factor alpha (TGF-Alpha), epidermal growth factor (EGF), insulinlike growth factor (IGF)-I, vascular endothelial growth factor (VEGF(165,189,121)), basic fibroblast growth factor (FGF)-2, EGF receptor (R), IGF-IRbeta, and FGFR-1 was studied in uterine leiomyomas and matched myometrial samples taken from seven women (42-47 years of age) in the proliferative phase of the menstrual cycle. Immunolocalization of growth factor peptides was accomplished with either monoclonal or polyclonal antibodies to the amino or carboxy terminus of growth factor peptides or their respective receptors, or against full-length recombinant growth factor. All reactions were conducted using the avidin-biotin complex method. Immunolocalization of TGF-alpha, EGF, EGF-R, IGF-I, IGF-IRbeta, FGF-2, FGFR-1, and VEGF was observed in the cytoplasm of smooth-muscle cells of leiomyomas and matched myometrium. The cytoplasm of vascular smooth-muscle cells expressed TGF-alpha, EGF, EGF-R, IGF-I, IGF-IRbeta, FGF-2, FGFR-1, and VEGF, whereas the vascular endothelium was positive for TGF-alpha, EGF, EGF-R, FGF-2, and FGFR-1 in both leiomyomas and matched myometria. Fibroblasts within the fibrous component of some leiomyomas were positive for IGF-I and FGF-2 and minimally positive for FGFR-1. In addition, the extracellular matrix of leiomyomas showed focal localization of FGF-2 and IGF-I in some tumors. When scores of intensity and percent positive staining were compared, IGF-IRbeta was significantly increased in the leiomyomas compared to matched myometria, whereas EGF was significantly decreased in the uterine leiomyomas compared to matched myometria. In summary, these data revealed growth factors to be expressed differentially in smooth muscle, vascular and fibroblastic cell types of leiomyomas and matched myometria. Specifically, IGF-IRbeta was significantly increased in leiomyomas; although a similar increase was seen with IGF-I peptide, statistical significance was not achieved. The EGF peptide was significantly decreased in the leiomyomas compared to matched myometrium. These data suggest that IGF-IRbeta and IGF-I peptide may be one of several growth factor/receptor pathways important in uterine leiomyoma growth during the proliferative phase of the menstrual cycle. In addition, decreased EGF may be secondary to the predominant estrogenic milieu present at time of sampling, as it has been proposed that progesterone, and not estrogen, may regulate EGF.
在月经周期增殖期，对7名年龄在42 - 47岁女性的子宫平滑肌瘤及配对的子宫肌层样本进行了转化生长因子α（TGF -α）、表皮生长因子（EGF）、胰岛素样生长因子（IGF）-I、血管内皮生长因子（VEGF(165,189,121)）、碱性成纤维细胞生长因子（FGF）-2、EGF受体（R）、IGF - IRβ和FGFR - 1的免疫定位研究。生长因子肽的免疫定位是通过针对生长因子肽或其各自受体的氨基或羧基末端的单克隆或多克隆抗体，或针对全长重组生长因子来完成的。所有反应均采用抗生物素蛋白 - 生物素复合物法进行。在平滑肌瘤和平滑肌配对的子宫肌层的平滑肌细胞胞质中观察到TGF -α、EGF、EGF - R、IGF - I、IGF - IRβ、FGF - 2、FGFR - 1和VEGF的免疫定位。血管平滑肌细胞的胞质表达TGF -α、EGF、EGF - R、IGF - I、IGF - IRβ、FGF - 2、FGFR - 1和VEGF，而在平滑肌瘤和配对的子宫肌层中，血管内皮对TGF -α、EGF、EGF - R、FGF - 2和FGFR - 1呈阳性。一些平滑肌瘤纤维成分中的成纤维细胞对IGF - I和FGF - 2呈阳性，对FGFR - 1呈弱阳性。此外，在一些肿瘤中，平滑肌瘤的细胞外基质显示FGF - 2和IGF - I的局灶性定位。当比较强度评分和阳性染色百分比时，与配对的子宫肌层相比，平滑肌瘤中的IGF - IRβ显著增加，而与配对的子宫肌层相比，子宫平滑肌瘤中的EGF显著减少。总之，这些数据表明生长因子在平滑肌瘤和平滑肌配对的子宫肌层的平滑肌、血管和成纤维细胞类型中差异表达。具体而言，平滑肌瘤中的IGF - IRβ显著增加；尽管IGF - I肽也有类似增加，但未达到统计学意义。与配对的子宫肌层相比，平滑肌瘤中的EGF肽显著减少。这些数据表明，IGF - IRβ和IGF - I肽可能是月经周期增殖期子宫平滑肌瘤生长中重要的几种生长因子/受体途径之一。此外，EGF减少可能是由于采样时存在的主要雌激素环境所致，因为有人提出是孕酮而非雌激素可能调节EGF。
