Bamberger Ana-Maria, Bamberger Christoph M, Aupers Solveigh, Milde-Langosch Karin, Löning Thomas, Makrigiannakis Antonis
Institute of Pathology, Department of Gynaecopathology, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Mol Hum Reprod. 2004 Apr;10(4):223-8. doi: 10.1093/molehr/gah011. Epub 2004 Feb 16.
The human placenta is a tissue with a unique capacity for rapid, but--as opposed to malignant tumours--tightly controlled proliferation and invasion capacity. The members of the activating protein-1 (AP-1) family of transcription factors are key regulators of cellular proliferation, differentiation and invasion processes in many systems and could, thus, play an important role in regulating these processes in the human placenta as well. In the present study, we used immunohistochemistry with specific antibodies against all members of the AP-1 family (c-Jun, JunB, JunD and c-Fos, FosB, Fra-1, Fra-2) to investigate their expression pattern and tissue localization in the human placenta. With the exception of c-Jun, which was expressed in a small fraction of villous cytotrophoblast nuclei and JunD, expressed in some syncytiotrophoblast nuclei, all other members of the AP-1 family were completely absent from villous cyto- and syncytiotrophoblast. Interestingly, most AP-1 factors were expressed in the intermediate (extravillous) trophoblast, with expression being strongest for JunD and Fra2 (100% of nuclei showing strong expression), followed by c-Jun (80% positive nuclei), c-Fos and FosB (50% positive nuclei). This was true for samples of both first trimester and later pregnancy. These data show that, in the human placenta, the AP-1 transcription factors are specifically expressed in the intermediate (extravillous) trophoblast, were they could be implicated in regulating proliferation, differentiation and/or expression of invasion-specific molecules, such as matrix metalloproteinases, which have been shown to be regulated by AP-1 in vitro and are expressed by the invasive trophoblast.
人胎盘是一种具有独特能力的组织,能够快速增殖和侵袭,但与恶性肿瘤不同的是,其增殖和侵袭能力受到严格控制。转录因子激活蛋白-1(AP-1)家族的成员是许多系统中细胞增殖、分化和侵袭过程的关键调节因子,因此在调节人胎盘的这些过程中也可能发挥重要作用。在本研究中,我们使用针对AP-1家族所有成员(c-Jun、JunB、JunD以及c-Fos、FosB、Fra-1、Fra-2)的特异性抗体进行免疫组织化学,以研究它们在人胎盘中的表达模式和组织定位。除了在一小部分绒毛细胞滋养层细胞核中表达的c-Jun以及在一些合体滋养层细胞核中表达的JunD外,AP-1家族的所有其他成员在绒毛细胞滋养层和合体滋养层中均完全缺失。有趣的是,大多数AP-1因子在中间型(绒毛外)滋养层中表达,其中JunD和Fra2的表达最强(100%的细胞核显示强表达),其次是c-Jun(80%的阳性细胞核)、c-Fos和FosB(50%的阳性细胞核)。早期妊娠和晚期妊娠的样本均如此。这些数据表明,在人胎盘中,AP-1转录因子在中间型(绒毛外)滋养层中特异性表达,它们可能参与调节增殖、分化和/或侵袭特异性分子(如基质金属蛋白酶)的表达,基质金属蛋白酶已被证明在体外受AP-1调节,并由侵袭性滋养层表达。