Human Wnt-13 is developmentally regulated during the differentiation of NTERA-2 pluripotent human embryonal carcinoma cells

Wakeman, Jane A.; Walsh, James; Andrews, Peter W.

doi:10.1038/sj.onc.1201942

Cited by 28 publications

(22 citation statements)

References 21 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although treatment of NTERA-2 cells with RA and HMBA gives rise to di erent types of terminally di erentiated cells, some common pathways are activated by these agents that may correlate with a commitment to di erentiation or loss of proliferative potential. For example, expression of the growth factors FGF4 and TGFa is downregulated and expression of Wnt-13 is induced following treatment with either RA or HMBA, consistent with the hypothesis that common extracellular signaling pathways are important for multiple NTERA-2 di erentiation programs (Miller et al, 1994;Wakeman et al, 1998). Down-regulation of the growth factors FGF4, TGFa, and TDGF-1 (CRIPTO) has been shown to contribute to the reduced proliferative and tumorigenic potential in di erentiated NTERA-2 cells (Baldassarre et al, 1996(Baldassarre et al, , 1997Baselga et al, 1993;Maerz et al, 1998).…”

Section: Introductionsupporting

confidence: 68%

The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells

et al. 2000

View full text Add to dashboard Cite

Section: Introductionsupporting

confidence: 68%

The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells

et al. 2000

View full text Add to dashboard Cite

“…Treatment of NTERA-2 cells with hexamethylene bisacetamide (HMBA) induces differentiation into a nonneuronal phenotype (2), whereas treatment with retinoic acid induces a neuronal phenotype (2,3). Although the pathways involved in these differentiation events are yet to be fully elucidated, it is interesting that these two compounds appear to activate common pathways, as suggested by both up-and downregulation of common downstream targets (4,5).…”

mentioning

confidence: 99%

The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation

Sacher

Bacco

Лунин

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-Å resolution. CREG forms a tight homodimeric complex, and CREG monomers display a β-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold.

show abstract

“…7). Thus, Wnt13, which is induced by retinoic acid in NTERA2 cells, 37 was similarly induced in TG11.nR and C10 cells, but not in 2102Ep. However, Mal and neuroD1, which are induced in NTERA2 cell 38,39 and were also induced in TG11.nR, were not induced in either 2102Ep or C10 cells.…”

Section: ϫ7mentioning

confidence: 99%

Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

et al. 2001

Self Cite

View full text Add to dashboard Cite

To investigate whether the failure of human EC cells that do not differentiate is due to the loss of key differentiationpermissive functions or the acquisition of specific inhibitory functions, we tested the ability to differentiate of 2 hybrids produced between a relatively nullipotent human EC cell line, 2102Ep, and a pluripotent human EC cell line NTERA2. Both hybrids, which exhibited an EC phenotype, were able to differentiate readily in response to retinoic acid. Furthermore, 1 hybrid produced a well-differentiated xenograft tumor, which contained, like the NTERA2 tumors, glandular structures, loose mesenchymal tissues and nodules of cartilage, after injection into a SCID mouse. Thus, the failure of 2102Ep EC cells to differentiate is recessive and due to the loss of a key gene function or functions. Nevertheless, the hybrids differed from the pluripotent NTERA2 line by failing to differentiate in neurons, indicating that 2102Ep cells also had acquired a specific, dominantly-acting, inhibitory mutation specific to the neural lineage. Furthermore, the expression of collagen II by one hybrid before and after induction with retinoic suggested a propensity for spontaneous differentiation not evident in the parental NTERA2 cells. Thus, the mechanisms that restrict the differentiation capacity of the nullipotent 2102Ep line are complex and include both recessive and dominant acting factors.

show abstract

Human Wnt-13 is developmentally regulated during the differentiation of NTERA-2 pluripotent human embryonal carcinoma cells

Cited by 28 publications

References 21 publications

The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells

The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells

The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation

Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

Contact Info

Product

Resources

About