Transcription Factor Gene <i>AP-2</i>γ Essential for Early Murine Development

Werling, Uwe; Schorle, Hubert

doi:10.1128/mcb.22.9.3149-3156.2002

Cited by 168 publications

(174 citation statements)

References 38 publications

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…6,7 AP-2g-deficient embryos die due to a lack of proliferation of trophectoderm-derived extraembryonic tissues. 7 Furthermore, studies on mice transgenic for AP-2g reveal a role in mammary gland tumorigenesis. 8 There, forced overexpression leads to a block of differentiation 8 as well as enhanced tumor progression in a double transgenic model.…”

Section: Discussionmentioning

confidence: 99%

“…5 AP-2g is essential for mammalian embryonic development because embryonic trophectodermal cells fail to proliferate in AP-2g knockout mice. 6,7 In transgenic studies, overexpression of AP-2g impaired differentiation of epithelial cells of the mammary gland and the seminal vesicle. 8 Besides trophoblastic and neuroectodermal lineage, AP-2g can be detected in lung, testis and ovary.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transcription factor AP‐2γ, a novel marker of gonocytes and seminomatous germ cell tumors

Pauls

Jäger

Weber

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

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-2g is expressed in gonocytes at weeks 12-37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP-2g 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-2g from the 12th to 37th week of gestation was observed. Furthermore, AP-2g was expressed abundantly in 25/25 IGCNUs, 52/53 testicular seminomas, 10/10 metastatic seminomas, 9/9 extragonadal seminomas and 5/5 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-2g. The expression pattern of AP-2g, 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-2g immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide. ' 2005 Wiley-Liss, Inc.Key words: AP-2g; gonocyte; neoplastic; seminoma; germ cell tumor The most abundant malignancies among men aged 17-45 are GCTs. 1 They comprise a heterogeneous group of neoplasms in terms of their histology, marker expression and age at manifestation. First described by Skakkebaek in 1972, the common precursor lesion of all GCTs, IGCNU (CIS, TIN, IGCN), arises from transformation of a gonocyte. 2,3 Markers commonly used for immunohistology, such as OCT3/4, PLAP and c-KIT, are expressed in gonocytes as well as IGCNUs and some stages of GCT, further supporting this model. TFAP2C belongs to a family of 5 closely related genes that are involved in the morphogenesis of craniofacial, urogenital, neural crest and placental tissues. 4 AP-2 transcription factors are believed to regulate the expression of several genes involved in cell growth and differentiation during development. 5 AP-2g is essential for mammalian embryonic development because embryonic trophectodermal cells fail to proliferate in AP-2g knockout mice. 6,7 In transgenic studies, overexpression of AP-2g impaired differentiation of epithelial cells of the mammary gland and the seminal vesicle. 8 Besides trophoblastic and neuroectodermal lineage, AP-2g can be detected in lung, testis and ovary. 9,10 In human tumors, AP-2g is upregulated in certain stages of melanoma 11 and breast cancer. 12,13 In the present study, we investigated the expression of AP-2...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transcription factor AP‐2γ, a novel marker of gonocytes and seminomatous germ cell tumors

Pauls

Jäger

Weber

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…AP-2␣ is a member of a small family of "basic-helix-span-helix" transcription factors important for many aspects of vertebrate development (Schorle et al, 1996;Zhang et al, 1996;Moser et al, 1997;Nottoli et al, 1998;Hilger-Eversheim et al, 2000;Satoda et al, 2000;Auman et al, 2002;Werling and Schorle, 2002;Mani et al, 2005). The transcription factor AP-2␣, encoded by Tcfap2a in mouse and TFAP2A in human, is expressed in both the developing face and limbs (Mitchell et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

Donner

Williams

2006

Developmental Dynamics

View full text Add to dashboard Cite

The AP-2 transcription factor family is linked with development of the head and limbs in both vertebrate and invertebrate species. Recent evidence has also implicated this gene family in the evolution of the neural crest in chordates, a critical step that allowed the development and elaboration of the vertebrate craniofacial skeleton. In mice, the inappropriate embryonic expression of one particular AP-2 gene, Tcfap2a, encoding AP-2␣, results in multiple developmental abnormalities, including craniofacial and limb defects. Thus, Tcfap2a provides a valuable genetic resource to analyze the regulatory hierarchy responsible for the evolution and development of the face and limbs. Previous studies have identified a 2-kilobase intronic region of both the mouse and human AP-2␣ locus that directs expression of a linked LacZ transgene to the facial processes and the distal mesenchyme of the limb bud in transgenic mice. Further analysis identified two highly conserved regions of ϳ200 -400 bp within this tissue-specific enhancer. We have now initiated a transgenic and biochemical analysis of the most important of these highly conserved regions. Our analysis indicates that although the sequences regulating face and limb expression have been integrated into a single enhancer, different cis-acting sequences ultimately control these two expression domains. Moreover, these studies demonstrate that a conserved STAT binding site provides a major contribution to the expression of Tcfap2a in the facial prominences. Developmental Dynamics 235: 1358 -1370, 2006.

show abstract

“…AP-2␤-deficient mice complete embryogenesis, but die shortly after birth due to impaired kidney function (Moser et al, 1997b(Moser et al, , 2003. Finally, AP-2␥ mutant embryos die very early after gastrulation as a result of defective placental development (Auman et al, 2002;Werling and Schorle, 2002).…”

Section: Introductionmentioning

confidence: 99%

Identification and embryonic expression of a new AP‐2 transcription factor, AP‐2ϵ

Wang¹,

Vaupel²,

Buettner³

et al. 2004

Developmental Dynamics

View full text Add to dashboard Cite

Transcription Factor Gene AP-2γ Essential for Early Murine Development

Cited by 168 publications

References 38 publications

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

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

Identification and embryonic expression of a new AP‐2 transcription factor, AP‐2ϵ

Contact Info

Product

Resources

About