Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2

Zhang, Jian; Hagopian-Donaldson, Stephanie; Serbedzija, George N.; Elsemore, Jennifer; Plehn-Dujowich, Debora; McMahon, Andrew P.; Flavell, Richard A.; Williams, Trevor

doi:10.1038/381238a0

Cited by 579 publications

(510 citation statements)

References 25 publications

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“…Indeed, AP-2 proteins regulate a number of genes related to epithelial cell di erentiation, like p21 waf/cip (Zeng et al, 1997), Ecadherin (Hennig et al, 1996), MXI1 (Benson et al, 1999) and ER-a itself (de Coninck et al, 1995) and AP-2 knock-out mice show several di erentiation defects in tissues of neuroectodermal origin and in kidney (Zhang et al, 1996;Schorle et al, 1996;Moser et al, 1997). On the contrary, the action of oestrogen on mammary cells is mitogenic.…”

Section: Discussionmentioning

confidence: 99%

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

et al. 2000

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Transcription of the ERBB2 oncogene is repressed by oestrogen in human breast cancer cells. We show that a 218 bp fragment of the human ERBB2 gene promoter is responsive to oestrogen in transient transfection in ZR75.1 and SKBR.3 cells when the oestrogen receptor is expressed. Deletion analysis of this fragment shows that a sequence located at the 5' end, which is known to mediate ERBB2 overexpression in breast cancer, is also responsible for the oestrogen response. This sequence binds AP-2 transcription factors and appears functionally identical to an element of the oestrogen-dependent enhancer described in the ®rst intron of human ERBB2. We observed that oestrogen treatment down-regulates expression of AP-2 proteins but does not a ect the DNA binding activity of AP-2. Constitutive expression of AP2b or AP-2g, but not AP-2a, abrogates the estrogenic repression. Our results demonstrate that AP-2 transcription factors are implicated in the oestrogenic regulation of ERBB2 gene expression and suggest a complex interplay involving the di erent AP-2 isoforms and other unidenti®ed factors. Oncogene (2000) 19, 280 ± 288.

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Section: Discussionmentioning

confidence: 99%

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

et al. 2000

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“…During mouse embryogenesis, AP-2a, AP-2b and AP2g are expressed strongly in the neural crest cells, which also participate in the formation of many vertebrate head structures (Hall, 1988). AP-2a null mice die perinatally with cranio-abdominoschisis and severe dismorphogenesis of the face, skull, and sensory organs (Schorle et al, 1996;Zhang et al, 1996).…”

Section: Expression Of Dap-2 During Drosophila Embryonic Development mentioning

confidence: 99%

“…This was con®rmed by generating mice containing a homozygous disruption of the AP-2a or AP-2b gene. Histopathological examination of AP-2a null mice revealed severe abnormalities, particularly anencephaly, cranofacial defects, failure to close the ventral body wall, causing perinatal death (Schorle et al, 1996;Zhang et al, 1996). AP-2b null mice exhibit enhanced apoptotic cell death of renal epithelial cells and die by postnatal day 1 and 2 because of polycystic kidney disease (Moser et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor

et al. 1998

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The AP-2 family of transcription factors (AP-2a, AP-2b and AP-2g) is temporally and spatially regulated in mammals and has also been implicated in oncogenesis. Here we report the isolation of genomic and cDNA clones encoding the Drosophila homologue of AP-2, designated DAP-2. The predicted amino acid sequence exhibits 42 ± 45% overall identity with the vertebrate AP-2 proteins. A sequence of 107 amino acids within the DNA binding and dimerization domain of the vertebrate AP-2 proteins is highly conserved (90 ± 92%) with the DAP-2 homologue. An in vitro translation product of DAP-2 cDNA binds speci®cally to AP-2 consensus binding sites. DAP-2 was also shown to be functionally conserved in vivo because transient transfection of a DAP-2 expression plasmid activated transcription through AP-2 binding sites in both mammalian and Drosophila cell lines. DAP-2 is expressed during early embryogenesis and DAP-2 transcripts are also detected in the adult. Whole-mount in situ hybridizations demonstrated that DAP-2 is expressed initially at stage 9 of Drosophila embryonic development and that DAP-2 transcripts are detected in regions of the brain, eyeantennal disc, optical lobe, antenno-maxillary complex, and in a subset of cells of the ventral nerve cord. The cloning of DAP-2 and the identi®cation of the DAP-2 expression pattern during embryogenesis provides a starting point to address the function of AP-2 during di erentiation and development in a well understood model system.

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“…In the adult mammary gland, expression of AP-2alpha, AP-2beta, and AP-2gamma has been documented. 6,7 Although highlighting the importance of AP-2 genes, the embryonic lethal phenotypes of mice lacking AP-2alpha, AP-2beta, or AP-2gamma [8][9][10][11] have so far precluded the analysis of their role in mammary development and function. Recently published gene-overexpression studies in transgenic mice suggest that both AP-2alpha and AP-2gamma may control proliferation, apoptosis and differentiation of mammary epithelial cells.…”

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confidence: 99%

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

et al. 2005

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Although transcription factors AP-2alpha and AP-2gamma have been implicated in the control of estrogen receptor (ER) and ErbB-2, their impact for breast cancer is still controversial. To better understand the role of AP-2 proteins in mammary neoplasia, the analysis of their spatial expression pattern in normal breast and breast cancer is required. A total of 51 specimens of female breast cancer patients and a tissue microarray containing 93 additional female breast cancer cases were immunohistochemically stained for AP-2alpha, AP2gamma, ER and ErbB-2. In 70 cases of the tissue microarray, survival data comprising a period of up to 30 years were present. In non-neoplastic breast tissue, AP-2alpha was expressed in the inner glandular cell layer while AP-2gamma was expressed in the outer myoepithelial cell layer. Ductal carcinoma in situ revealed strongly AP-2alpha-positive tumor cells surrounded by a layer of AP-2gamma-positive myoepithelial cells. In invasive carcinoma, expression of AP-2alpha and AP-2gamma was variable. High expression of ER and AP2alpha showed better survival rates than low expression of these markers. AP-2gamma expression had no effect on survival. These results for the first time reveal a distinct spatial expression pattern of AP-2alpha and AP-2gamma in normal breast and in ductal carcinoma in situ with specific AP-2gamma expression in myoepithelium. High ER and AP-2alpha expression in invasive breast cancer showed favorable survival rates. Therefore, AP-2alpha expression seems to be associated with better prognosis of breast cancer. AP-2gamma expression has no influence on survival reflecting that myoepithelial cells are not involved in the neoplastic process.

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Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2

Cited by 579 publications

References 25 publications

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor

Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer

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