Bowen Nathan J, Logani Sanjay, Dickerson Erin B, Kapa Laura B, Akhtar Mariam, Benigno Benedict B, McDonald John F
School of Biology, Georgia Institute of Technology, and Ovarian Cancer Institute, Atlanta, GA 30332, USA.
Gynecol Oncol. 2007 Feb;104(2):331-7. doi: 10.1016/j.ygyno.2006.08.052. Epub 2006 Oct 24.
Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo complex differentiation to form distinguishable phenotypes resembling those of the epithelia of the female urogenital regions. While previous studies have implicated regulatory developmental homeobox (HOX) genes in this process, other factors responsible for this differentiation are largely unknown. Aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, prompting us to initiate the molecular characterization of this master regulatory gene in ovarian cancer development.
Immunohistochemistry, immunoblotting and RT-PCR were used to investigate the presence of PAX8 and its protein products in epithelial ovarian cancer subtypes, normal ovarian surface epithelia, ovarian inclusion cysts and normal endosalpingeal epithelia.
In this report, we confirm microarray results indicating that the transcription factor, PAX8, is highly expressed in epithelial ovarian cancer but absent from the precursor ovarian surface epithelia of healthy individuals. Furthermore, we report that PAX8 is localized to the nucleus of non-ciliated epithelia in simple ovarian epithelial inclusion cysts and in three epithelial ovarian cancer subtypes (serous, endometrioid and clear cell). We also determined that PAX8 is expressed in the non-ciliated, secretory cells of healthy fallopian tube mucosal linings but not in the adjacent ciliated epithelia.
These findings support the hypothesis that PAX8 plays parallel roles in the development of epithelial ovarian cancer and in the developmental differentiation of coelomic epithelia into endosalpingeal epithelia.
上皮性卵巢癌起源于卵巢表面上皮，后者经历复杂分化形成与女性泌尿生殖区域上皮相似的可区分表型。虽然先前的研究表明调控发育同源框（HOX）基因参与了这一过程，但导致这种分化的其他因素在很大程度上尚不清楚。已有报道称PAX8在上皮性卵巢癌中存在异常转录表达，这促使我们对该主要调控基因在卵巢癌发生发展中的分子特征进行研究。
采用免疫组织化学、免疫印迹和逆转录聚合酶链反应（RT-PCR）来研究PAX8及其蛋白产物在上皮性卵巢癌亚型、正常卵巢表面上皮、卵巢包涵囊肿和正常输卵管内膜上皮中的存在情况。
在本报告中，我们证实了微阵列结果，表明转录因子PAX8在上皮性卵巢癌中高表达，但在健康个体的卵巢表面上皮前体中不存在。此外，我们报告PAX8定位于单纯性卵巢上皮包涵囊肿以及三种上皮性卵巢癌亚型（浆液性、子宫内膜样和透明细胞型）的非纤毛上皮细胞核中。我们还确定PAX8在健康输卵管黏膜衬里的非纤毛分泌细胞中表达，但在相邻的纤毛上皮中不表达。
这些发现支持了PAX8在上皮性卵巢癌发生发展以及体腔上皮向输卵管内膜上皮发育分化过程中发挥平行作用的假说。
