Biomedical subjects

Mélanie Béland

Publications and source records attributed to Mélanie Béland.

3 recordsLinked to original sources

PubMed2006

[PAX gene function during kidney tumorigenesis: a comparative approach].

The rising incidence of cancers affecting the kidney emphasizes the need to identify the molecular pathways involved in the initiation and progression of kidney tumors in order to counter this phenomenon. For many years, genes belonging to the PAX family have been the focus of intensive studies in the fields of organogenesis and tumorigenesis. PAX2 and PAX8 encode transcription factors essential for embryonic kidney development. Transcriptionnal repression of these factors is, however, required to allow terminal differentiation of renal epithelia. In human, maintenance and reactivation of PAX2/8 expression are frequently observed in cases of Wilm's tumor and renal cell carcinoma. The precise role of PAX2/8 in kidney cancer is still elusive but results from several studies suggest the exertion of common functions during organogenesis and tumorigenesis of the kidney. Moreover, many members of the PAX family are involved in similar cellular processes such as differentiation/proliferation, motility and apoptosis. Thus, by comparing the functions exerted by PAX factors in several types of cancers should be useful to better define the specific contribution of PAX2/8 to kidney tumorigenesis.

Eye Proteins↗

PubMed2005

Chicken ovalbumin upstream promoter-transcription factor members repress retinoic acid-induced Cdx1 expression.

It is well established that Hox genes are key players in specifying positional identity along the anterior-posterior axis and are targets of diverse transcription factors implicated in axial patterning. Members of the CDX family (CDX1, -2, and -4) are among such effectors of Hox expression as pertains to vertebral patterning in the mouse. Cdx members are themselves targets of signaling molecules that are also implicated in axial patterning, including retinoic acid (RA) and certain members of Wnt and fibroblast growth factor families. In this regard, we have previously shown that, in the mouse, Cdx1 is directly regulated by RA at the late primitive streak stage (embryonic day (E) 7.5) through a RA response element in the proximal Cdx1 promoter. At E8.5, Cdx1 expression remains essentially limited to the posterior embryo. RA, however, is excluded from the caudal embryo at this later stage, but is found in a more anterior domain encompassing the prospective trunk region. These observations suggest the existence of a repressor mechanism that prevents expression of Cdx1 in these anterior domains of retinoid signaling at E8.5. In the present study, we present evidence suggesting that chicken ovalbumin upstream promoter-transcription factor (COUP-TF) members antagonize RA-induced Cdx1 expression by competing with retinoid X receptor-retinoic acid receptor heterodimers for binding to the Cdx1 RA response element. Consistent with this, in situ hybridization analysis revealed that COUP-TFs are highly expressed in the anterior embryo in domains where Cdx1 transcripts are excluded. Together with other data, these findings suggest a model by which COUP-TF expression is induced by RA in the trunk region as a negative feedback mechanism to restrict Cdx1 expression to the caudal embryo.

Animals↗

PubMed2004

Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex.

The Cdx1 gene product is essential for normal anterior-posterior vertebral patterning. Expression of Cdx1 is regulated by several pathways implicated in anterior-posterior patterning events, including retinoid and Wnt signaling. We have previously shown that retinoic acid plays a key role in early stages of Cdx1 expression at embryonic day 7.5 (E7.5), while both Wnt3a signaling and an autoregulatory loop, dependent on Cdx1 itself, are involved in later stages of expression (E8.5 to E9.5). This autoregulation is reflected by the ability of Cdx1 to affect expression from proximal Cdx1 promoter sequences in tissue culture. However, this region is devoid of a demonstrable Cdx response element(s). We have now found that Cdx1 and LEF1, a nuclear effector of Wnt signaling, synergize to induce expression from the Cdx1 promoter through previously documented LEF/T-cell factor response elements. We also found a direct physical interaction between the homeodomain of Cdx1 and the B box of LEF1, suggesting a basis for this synergy. Consistent with these observations, analysis of Cdx1 Wnt3a(vt) compound mutants demonstrated that Wnt and Cdx1 converged on Cdx1 expression and vertebral patterning in vivo. Further data suggest that Cdx-high-mobility group box interactions might be involved in a number of additional pathways.

Animals↗