Cesen-Cummings K, Copland J A, Barrett J C, Walker C L, Davis B J
Laboratory of Women's Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Environ Health Perspect. 2000 Oct;108 Suppl 5:817-20. doi: 10.1289/ehp.00108s5817.
Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecologic neoplasm in women. Studies with surgically resected human tissues and primary cultures have revealed that several genes are differentially expressed in leiomyomas compared to matched normal myometrium. An estrogen-driven pattern of gene expression in leiomyomas, similar to that seen in normal myometrium during pregnancy and parturition, is associated with a persistent inappropriate response of neoplastic myometrial smooth muscle cells to ovarian hormones. This is possibly due to aberrant expression levels or signaling via estrogen and progesterone receptors. We propose the hypothesis that uterine leiomyomas mimic a differentiated myometrial cell at pregnancy and exhibit a hypersensitivity to sex steroid hormones that prevents the cells from responding to normal apoptotic or dedifferentiation signals and from returning to a nongravid phenotype. Support of this hypothesis is derived from experimental studies in female Eker rats that develop uterine leiomyomas with many similarities to the human disease. Our hypothesis accounts for the benign nature of these tumors and their high incidence in women during the reproductive years. By identifying the factors that participate in parturition and involution of the pregnant myometrium, we may better define uterine leiomyomas and thus identify novel targets for therapeutic strategies to treat these tumors.
子宫肌瘤是子宫的良性平滑肌肿瘤，是女性最常见的妇科肿瘤。对手术切除的人体组织和原代培养物的研究表明，与匹配的正常子宫肌层相比，子宫肌瘤中有几种基因表达存在差异。子宫肌瘤中雌激素驱动的基因表达模式，类似于正常子宫肌层在妊娠和分娩期间的模式，与肿瘤性子宫肌层平滑肌细胞对卵巢激素的持续不适当反应有关。这可能是由于雌激素和孕激素受体的表达水平异常或信号传导异常所致。我们提出一个假说，即子宫平滑肌瘤模仿妊娠时分化的子宫肌层细胞，并对性甾体激素表现出超敏反应，从而阻止细胞对正常的凋亡或去分化信号作出反应，也阻止细胞恢复到非妊娠表型。对雌性艾克大鼠的实验研究支持了这一假说，这些大鼠会发生与人类疾病有许多相似之处的子宫平滑肌瘤。我们的假说解释了这些肿瘤的良性性质及其在育龄女性中的高发病率。通过确定参与妊娠子宫肌层分娩和 involution（此处原文可能有误，推测可能是 involution，意为退化、复旧）的因素，我们可以更好地定义子宫平滑肌瘤，从而确定治疗这些肿瘤的治疗策略的新靶点。
