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TRAF4, at the Crossroad between Morphogenesis and Cancer.

Rousseau A, Rio MC, Alpy F - Cancers (Basel) (2011)

Bottom Line: TRAF4 encodes an adaptor protein that belongs to the TRAF protein family.While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes.Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U964 INSERM, Université de Strasbourg, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France. fabien.alpy@igbmc.fr.

ABSTRACT
Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

No MeSH data available.


Related in: MedlinePlus

TRAF4 expression in normal breast and cancerous tissues. Immunohistochemistry of TRAF4 expression (brown) in normal breast (a), in situ carcinoma (b) and invasive carcinoma (c). Note that TRAF4 localization is modified from a predominantly membrane-associated presence in normal breast (a, arrows) to a mainly cytoplasmic presence in invasive tumor cells (c); in situ carcinomas represent an intermediate state in which TRAF4 remains associated focally with the membrane (b, arrows).
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f2-cancers-03-02734: TRAF4 expression in normal breast and cancerous tissues. Immunohistochemistry of TRAF4 expression (brown) in normal breast (a), in situ carcinoma (b) and invasive carcinoma (c). Note that TRAF4 localization is modified from a predominantly membrane-associated presence in normal breast (a, arrows) to a mainly cytoplasmic presence in invasive tumor cells (c); in situ carcinomas represent an intermediate state in which TRAF4 remains associated focally with the membrane (b, arrows).

Mentions: TRAF4 was initially identified in breast cancer from a differential screen between metastatic lymph nodes and benign fibrodenomas biopsies [3]. TRAF4 is located in the q11.2 region of the long arm of chromosome 17, close to the ErbB2 oncogene [3,4]. TRAF4 mRNA was shown to be overexpressed in approximately one-quarter of breast cancers as a consequence of gene amplification [40]. This was subsequently confirmed by comparative genomic hybridization (CGH) and cDNA microarrays [41-43]. Interestingly TRAF4 overexpression is not limited to breast cancers. Indeed, it has been found in 43% of 623 human tumor samples from lung, ovary, prostate and colon among others [44]. In this latter study, TRAF4 overexpression is caused by gene amplification in about one-third of the tumors. TRAF4 protein overexpression is therefore a common feature of human cancers. Accordingly, TRAF4 was identified in a meta-analysis of 40 independent microarray studies as one of the 67 genes whose overexpression is characteristic of carcinomas [45]. TRAF4 overexpression is always observed in cancer cells and never in stromal cells. Its subcellular localization is variable and is cytoplasmic and/or membrane-associated (Figure 2), but nuclear localization is also observed in about 20% of TRAF4-positive tumors [4,44]. Interestingly, the membrane-association of TRAF4 seems to be correlated with tumor cell polarity and differentiation (Figure 2). These studies strongly suggest that TRAF4 plays an important role in carcinogenesis. Interestingly, in breast cancers, TRAF4 amplification can occur independently of ErbB2 amplification suggesting that TRAF4 may be the target of a more centromeric amplicon than the one involving ErbB2 [40,44]. Collectively, these data suggest that TRAF4 is not only a marker of human carcinomas, but also a candidate oncogene.


TRAF4, at the Crossroad between Morphogenesis and Cancer.

Rousseau A, Rio MC, Alpy F - Cancers (Basel) (2011)

TRAF4 expression in normal breast and cancerous tissues. Immunohistochemistry of TRAF4 expression (brown) in normal breast (a), in situ carcinoma (b) and invasive carcinoma (c). Note that TRAF4 localization is modified from a predominantly membrane-associated presence in normal breast (a, arrows) to a mainly cytoplasmic presence in invasive tumor cells (c); in situ carcinomas represent an intermediate state in which TRAF4 remains associated focally with the membrane (b, arrows).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757440&req=5

f2-cancers-03-02734: TRAF4 expression in normal breast and cancerous tissues. Immunohistochemistry of TRAF4 expression (brown) in normal breast (a), in situ carcinoma (b) and invasive carcinoma (c). Note that TRAF4 localization is modified from a predominantly membrane-associated presence in normal breast (a, arrows) to a mainly cytoplasmic presence in invasive tumor cells (c); in situ carcinomas represent an intermediate state in which TRAF4 remains associated focally with the membrane (b, arrows).
Mentions: TRAF4 was initially identified in breast cancer from a differential screen between metastatic lymph nodes and benign fibrodenomas biopsies [3]. TRAF4 is located in the q11.2 region of the long arm of chromosome 17, close to the ErbB2 oncogene [3,4]. TRAF4 mRNA was shown to be overexpressed in approximately one-quarter of breast cancers as a consequence of gene amplification [40]. This was subsequently confirmed by comparative genomic hybridization (CGH) and cDNA microarrays [41-43]. Interestingly TRAF4 overexpression is not limited to breast cancers. Indeed, it has been found in 43% of 623 human tumor samples from lung, ovary, prostate and colon among others [44]. In this latter study, TRAF4 overexpression is caused by gene amplification in about one-third of the tumors. TRAF4 protein overexpression is therefore a common feature of human cancers. Accordingly, TRAF4 was identified in a meta-analysis of 40 independent microarray studies as one of the 67 genes whose overexpression is characteristic of carcinomas [45]. TRAF4 overexpression is always observed in cancer cells and never in stromal cells. Its subcellular localization is variable and is cytoplasmic and/or membrane-associated (Figure 2), but nuclear localization is also observed in about 20% of TRAF4-positive tumors [4,44]. Interestingly, the membrane-association of TRAF4 seems to be correlated with tumor cell polarity and differentiation (Figure 2). These studies strongly suggest that TRAF4 plays an important role in carcinogenesis. Interestingly, in breast cancers, TRAF4 amplification can occur independently of ErbB2 amplification suggesting that TRAF4 may be the target of a more centromeric amplicon than the one involving ErbB2 [40,44]. Collectively, these data suggest that TRAF4 is not only a marker of human carcinomas, but also a candidate oncogene.

Bottom Line: TRAF4 encodes an adaptor protein that belongs to the TRAF protein family.While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes.Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U964 INSERM, Université de Strasbourg, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France. fabien.alpy@igbmc.fr.

ABSTRACT
Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

No MeSH data available.


Related in: MedlinePlus