Transcription factor AP-2γ, a novel marker of gonocytes and seminomatous germ cell tumors
Transcription factor AP-2γ, a novel marker of gonocytes and seminomatous germ cell tumors
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DOI：
10.1002/ijc.20913
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发表时间：
2005-06-20
影响因子：
6.4
通讯作者：
Schorle, H
中科院分区：
文献类型：
--
作者：
Pauls, K;Jäger, R;Schorle, H
大多数生殖细胞肿瘤（GCT）源自管内生殖细胞肿瘤（IGCNU，也称为原位癌），其被认为源自转化的胎儿生殖细胞（生殖母细胞）。然而，参与 IGCNU 形成的分子途径的性质仍然难以捉摸。因此，鉴定新的癌胎儿标志物是进一步了解该肿瘤实体病因学的重要先决条件。在本研究中，我们发现人类 AP-2 γ 在妊娠第 12-37 周的生殖母细胞中表达，表明该转录因子在胎儿生殖细胞发育中的作用。 AP-2 gamma 和 c-KIT（AP-2 转录因子的已知靶标）在生殖母细胞中共表达，使得直接调节成为可能。随着胎儿睾丸分化的增加，从妊娠第12周至第37周观察到AP-2γ逐渐下调。此外，AP-2γ在25/25个IGCNU、52153个睾丸精原细胞瘤、10/10个转移性精原细胞瘤、9/9个性腺外精原细胞瘤和515个无性细胞瘤中大量表达。在胚胎癌和绒毛膜癌中，仅观察到局灶染色。精原细胞瘤、畸胎瘤和卵黄囊肿瘤以及正常成人睾丸和各种对照组织的 AP-2 γ 呈阴性。 AP-2 γ 的表达模式与其他癌胎儿标记物一样，支持 IGCNU 和生殖细胞肿瘤的生殖细胞起源模型。最后，我们的结果为应用 AP-2 γ 免疫组织化学检测 GCT 提供了基础，GCT 是一种在全球男性人群中发病率稳步增长的肿瘤实体。 (c) 2005 年 Wiley-Liss, Inc.
Most germ cell tumors (GCTs) arise from intratubular germ cell neoplasias (IGCNUs, also referred to as carcinoma in situ), which are thought to originate from a transformed fetal germ cell, the gonocyte. However, the nature of the molecular pathways involved in IGCNU formation remains elusive. Therefore, identification of novel oncofetal markers is an important prerequisite to further our understanding of the etiology of this tumor entity. In the present study, we show that in humans AP-2 gamma is expressed in gonocytes at weeks 12-37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP-2 gamma and c-KIT, a known target of AP-2 transcription factors, were coexpressed in gonocytes, making a direct regulation possible. With increasing differentiation of fetal testis, gradual downregulation of AP-2 gamma from the 12th to 37th week of gestation was observed. Furthermore, AP-2 gamma was expressed abundantly in 25/25 IGCNUs, 52153 testicular seminomas, 10/10 metastatic seminomas, 9/9 extragonadal seminomas and 515 dysgerminomas. In embryonal carcinomas and choriocarcinomas, focal staining only was observed. Spermatocytic seminomas, teratomas and yolk sac tumors as well as normal adult testis and various control tissues were negative for AP-2 gamma. The expression pattern of AP-2 gamma, like that of other oncofetal markers, supports the model of a gonocytal origin of IGCNUs and germ cell tumors. Finally, our results provide the basis for applying AP-2 gamma immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide. (c) 2005 Wiley-Liss, Inc.