Sourla A, Polychronakos C, Zeng W R, Nepveu A, Kukuvitis A, Naud F, Koutsilieris M
Molecular Endocrinology, Centre Hospitalier de 1' Universite Laval, St. Foy, Canada.
Cancer Res. 1996 Jul 1;56(13):3123-8.
We analyzed the expression of plasminogen activator inhibitor 1 (PAI-1) in 16 leiomyomas and adjacent myometrium of women who underwent a hysterectomy while in the proliferative (n = 8) and secretory phases (n = 8) of the menstrual cycle. We localized the PAI-1 and its mRNA expression in smooth muscle and vessel endothelial cells of uterine tissues using immunocytochemistry and in situ hybridization. The expression of PAI-1 mRNA was higher in 11 (68.75%) of 16 leiomyomas compared with the adjacent myometrium (leiomyoma/myometrium ratio, 1.4-3.0; mean, 2.045). The leiomyoma:myometrium ratio of PAI-1 mRNA expression did not change during the proliferative (Phase I) and secretory (Phase II) phases of the menstrual cycle. In the remaining five samples, the leiomyoma:myometrium ratio of PAI-1 mRNA expression was close to 1 (0.8-1.2; mean, 0.92). Because the locus of the PAI-1 gene is on chromosome 7q22, we screened for loss of heterozygosity (LOH) in these samples using the PAI-1 marker and D7S471, an anonymous marker 12 cM telomeric to PAI-1. Four of five samples with low leiomyoma:myometrium ratio had LOH for the PAI-1 and/or D7S471 markers. The fifth sample demonstrated a noninformative analysis for these markers but had LOH for the D7S515, D7S666, and D7S518 markers, all centromeric to PAI-1. Because del(7)(q22), associated with a relatively low PAI-1 mRNA expression, can deregulate matrix proteinases and growth factors' activity in leiomyomas, it is conceivable that del(7)(q22) results in heterogeneous leiomyoma biology.
我们分析了16例接受子宫切除术的女性的平滑肌瘤及相邻肌层中纤溶酶原激活物抑制剂1（PAI-1）的表达情况，这些女性处于月经周期的增殖期（n = 8）和分泌期（n = 8）。我们采用免疫细胞化学和原位杂交技术，在子宫组织的平滑肌和血管内皮细胞中定位PAI-1及其mRNA表达。与相邻肌层相比，16例平滑肌瘤中有11例（68.75%）的PAI-1 mRNA表达更高（平滑肌瘤/肌层比值为1.4 - 3.0；平均为2.045）。月经周期的增殖期（I期）和分泌期（II期），PAI-1 mRNA表达的平滑肌瘤:肌层比值没有变化。在其余5个样本中，PAI-1 mRNA表达的平滑肌瘤:肌层比值接近1（0.8 - 1.2；平均为0.92）。由于PAI-1基因位于7号染色体q22上，我们使用PAI-1标记物和D7S471（PAI-1端粒方向12 cM处的一个匿名标记物）对这些样本进行杂合性缺失（LOH）筛查。平滑肌瘤:肌层比值低的5个样本中，有4个在PAI-1和/或D7S471标记物处存在LOH。第5个样本对这些标记物的分析无信息，但在PAI-1着丝粒方向的D7S515、D7S666和D7S518标记物处存在LOH。由于与相对较低的PAI-1 mRNA表达相关的del(7)(q22)可使平滑肌瘤中的基质蛋白酶和生长因子活性失调，因此可以推测del(7)(q22)导致了平滑肌瘤生物学特性的异质性。
