Tumor Necrosis Factor Receptor-associated Death Domain Protein Is Involved in the Neurotrophin Receptor-mediated Antiapoptotic Activity of Nerve Growth Factor in Breast Cancer Cells

Yazidi‐Belkoura, Ikram El; Adriaenssens, Éric; Dollé, Laurent; Descamps, Simon; Hondermarck, Hubert

doi:10.1074/jbc.m300631200

Cited by 66 publications

(54 citation statements)

References 25 publications

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“…NGF-stimulation induces proliferation of MCF-7 and MDA-MB-231 breast cancer cell lines [66] and protects MCF-7 cells from ceramide analog-induced apoptosis [67,68]. However, NGF did not display an effect on normal breast epithelial cells.…”

Section: The Role Of Bex Proteins In Breast Cancermentioning

confidence: 93%

“…Therefore, NGF-induced biological effects in breast cancer are highly dependent on receptor expression profile and activity. Activation of the NF-κB pathway by NGF through p75NTR is involved in protection against ceramide analog-induced apoptosis [67,68]. A subset of estrogen receptor positive breast cancer samples displayed elevated expression of BEX1 and BEX2 mRNA [69].…”

Section: The Role Of Bex Proteins In Breast Cancermentioning

confidence: 99%

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Brain-Expressed X-linked (BEX) proteins in human cancers

Kazi

Kabir

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The Brain-Expressed X-linked (BEX) family proteins are comprised of five human proteins including BEX1, BEX2, BEX3, BEX4 and BEX5. BEX family proteins are expressed in a wide range of tissues and are known to play a role in neuronal development. Recent studies suggest a role of BEX family proteins in cancers. BEX1 expression is lost in a subgroup of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Expression of BEX1 controls cell surface receptor signaling and restores imatinib response in resistant cells. BEX2 is overexpressed in a group of breast cancer patients and also in gliomas. Increased BEX2 expression led to enhanced NF-κB signaling as well as cell proliferation. Although BEX2 acts as tumor promoter in a subset of breast cancer, BEX3 expression displayed an opposite role. Overexpression of BEX3 resulted in inhibition of tumor formation in breast cancer mouse xenograft models. The role of BEX4 and BEX5 in cancer has not yet been defined. Collectively this suggests that BEX family members have distinct roles in cancers.While BEX1 and BEX3 act as a tumor suppressors, BEX2 seems to act as an oncogene.

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Section: The Role Of Bex Proteins In Breast Cancermentioning

confidence: 93%

Section: The Role Of Bex Proteins In Breast Cancermentioning

confidence: 99%

Brain-Expressed X-linked (BEX) proteins in human cancers

Kazi

Kabir

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…[11][12][13] Furthermore, there is a known interaction between the ceramide and NF-jB pathways. 14,15 For example ceramide, in addition to inducing cell death, activates an opposing NF-jB-dependent survival pathway leading to 2 different cell fates. 16,17 Besides the effect on apoptosis, ceramide also induces a G1-cell cycle arrest in cancer cells.…”

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confidence: 99%

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Naderi¹,

Liu²,

Bennett³

2010

Intl Journal of Cancer

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We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-jB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.

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“…14 However, the ratio between NGF:NGFR was reported to be of prognostic significance. 15 As the role of NGFR in breast cancer development and progression is not fully understood and conflicting results have been reported, [14][15][16][17] we decided to investigate the distribution of NGFR in breast tissue from various benign and malignant conditions and explore potential prognostic relationships. In a preliminary analysis, we and others 5 observed that NGFR showed a peculiar distribution, being restricted to myoepithelial cells, intralobular fibroblasts of terminal duct-lobular units, perivascular cells (vascular adventitia) and nerve bundles.…”

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confidence: 99%

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

et al. 2006

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Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without intrinsic tyrosine kinase activity, whose expression is not restricted to neural cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell growth and proliferation. NGFR expression was immunohistochemically analysed in normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions, in 22 tumours with myoepithelial differentiation and in two cohorts of breast cancer patients: a series of 245 invasive breast carcinomas studied with tissue microarrays and 37 high-grade invasive ductal carcinomas with basal-like immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for NGFR. Scattered NGFRpositive cells were observed in solid areas of six out of nine cases of hyperplasia of usual type, whereas in flat atypia, lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%) metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast carcinomas. NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (Po0.05), 14 (Po0.0001) and 17 (Po0.0005) and EGFR (Po0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, Po0.0001). NGFR showed a statistically significant association with longer disease-free (Po0.05) and overall survival (Po0.01) in the cohort of patients with basal-like carcinomas. This study demonstrates the usefulness of NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive lesions and myoepithelial differentiation in breast carcinomas. Furthermore, provisional data in a small number of basal-like breast carcinomas suggest that NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.

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Tumor Necrosis Factor Receptor-associated Death Domain Protein Is Involved in the Neurotrophin Receptor-mediated Antiapoptotic Activity of Nerve Growth Factor in Breast Cancer Cells

Cited by 66 publications

References 25 publications

Brain-Expressed X-linked (BEX) proteins in human cancers

Brain-Expressed X-linked (BEX) proteins in human cancers

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

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