Tennent B J, Shultz K L, Sundberg J P, Beamer W G
Jackson Laboratory, Bar Harbor, ME 04609.
Am J Obstet Gynecol. 1990 Aug;163(2):625-34. doi: 10.1016/0002-9378(90)91214-w.
A high incidence (27.5%; 174 of 633) of spontaneous, malignant ovarian granulosa cell tumors develop in (SWR x SWXJ-9)F1 hybrid females between 3 and 6 weeks. Granulosa cell tumors developed in predictable stages, starting as preneoplastic lesions appearing as hyperemic follicles on the ovarian surface. These follicles were characterized by hypertrophied theca, degenerating oocytes, and large fluid- or erythrocyte-filled antra lined by irregular masses of granulosa cells. Rapidly proliferating granulosa cells filled the antra and the theca/interstitial cells became more dysplastic as granulosa cell tumors developed. Thus the morphology of the preneoplastic lesion suggests that disturbed mechanisms for normal follicular development underlie granulosa cell tumor initiation. Estradiol treatment before but not after preneoplastic lesions appeared inhibited granulosa cell tumor formation. By 6 to 9 months 42% of these mice show metastases in major abdominal and thoracic organs. Thus this model can be experimentally analyzed both for mechanisms of granulosa cell tumor initiation and subsequent malignant progression.
在（SWR×SWXJ-9）F1杂交雌性小鼠3至6周龄时，自发性恶性卵巢颗粒细胞瘤的发病率很高（27.5%；633只中有174只）。颗粒细胞瘤按可预测的阶段发展，始于卵巢表面出现充血卵泡的癌前病变。这些卵泡的特征是卵泡膜肥大、卵母细胞退化，以及由不规则颗粒细胞团块衬里的充满液体或红细胞的大卵泡腔。随着颗粒细胞瘤的发展，快速增殖的颗粒细胞充满卵泡腔，卵泡膜/间质细胞变得更加发育异常。因此，癌前病变的形态表明，正常卵泡发育机制的紊乱是颗粒细胞瘤起始的基础。在癌前病变出现之前而非之后进行雌二醇治疗可抑制颗粒细胞瘤的形成。到6至9个月时，这些小鼠中有42%在主要腹部和胸部器官出现转移。因此，该模型可用于实验分析颗粒细胞瘤起始机制和随后的恶性进展。
