The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias.

Huebner, Kay; Isobe, Masaharu; Chao, Moses V.; Bothwell, Mark; Ross, Alonzo H.; Hoxie, James A.; Sehgal, Amita; Buck, C.R.; Lanahan, AA

doi:10.1073/pnas.83.5.1403

Cited by 82 publications

(24 citation statements)

References 36 publications

(47 reference statements)

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“…Human p75 NTR , also known as nerve growth factor receptor (NGFR), maps to 17q21 1 and encodes a 75 kDa cell surface receptor glycoprotein that binds with similar affinity to the neurotrophin family of growth factors. [2][3][4] It is now apparent that expression of NGFR is ubiquitous and not limited to the nervous system, 4 being expressed in mature nonneural cells such as perivascular cells, dental pulp cells, lymphoidal follicular dendritic cells, basal epithelium of oral mucosa and hair follicles, prostate basal cells and myoepithelial cells.…”

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

et al. 2006

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“…Human p75 neurotrophin receptor (p75NTR), which was known as nerve growth factor receptor, maps to 17q21 (1). The gene encodes a 75-kDa cell-surface receptor glycoprotein that binds with the neurotrophin family of growth factors (2).…”

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confidence: 99%

p75 Neurotrophin Receptor Inhibits Invasion and Metastasis of Gastric Cancer

Jin

Pan

et al. 2007

Molecular Cancer Research

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The p75 neurotrophin receptor (p75NTR) is a focus for study at present. However, its function in gastric cancer was not elucidated. Here, we investigated its relation with metastasis of gastric cancer. By immunohistochemistry, we found that the positive rate of p75NTR expression in metastatic gastric cancer was 15.09% (16 of 106), which was lower compared with nonmetastatic gastric cancer (64.15%; 68 of 106). The average staining score in nonmetastatic gastric cancer was significantly higher than in metastatic gastric cancer (1.21 F 0.35 versus 0.23 F 0.18; P < 0.01). p75NTR protein level was also lowly expressed in the highly liver-metastatic gastric cancer cell line XGC9811-L compared with other gastric cancer cell lines by Western blotting. It could also significantly inhibit the in vitro adhesive, invasive, and migratory and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45 by reducing urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 proteins and by increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein. Further studies showed that p75NTR could suppress the nuclear factor-KB (NF-KB) signal. SN50, a specific inhibitor of NF-KB, which could inhibit in vitro invasive and migratory abilities of gastric cancer cells, reduced expression of uPA and MMP9 proteins and increased expression of TIMP1 protein. Taken together, p75NTR had the function of inhibiting the invasive and metastatic abilities of gastric cancer cells, which was mediated, at least partially, by down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein via the NF-KB signal transduction pathway.Our studies suggested that p75NTR may be used as a new potential therapeutic target in metastatic gastric cancer. (Mol Cancer Res 2007;5(5):423 -33)

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“…11 The human p75 NTR gene locus has also been mapped closely distal to 17q21. 12 Interestingly, microcell-mediated chromosomal transfer experiments have identified a tumor-suppressor gene associated with prostate cancer in the region 17q12-q22, 13 and a metastasis-suppressor gene for prostate cancer on chromosome 17. 14,15 Although the BRCA1 tumor-suppressor gene has been localized to this region, not all of the prostate tumor-suppressor activity in the region of 17q21 has been fully accounted for by the BRCA1 gene, 16 so that BRCA1 itself appears to play only a minor role in prostate cancer development.…”

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“…17 The NM23 metastasissuppressor gene also localizes to 17q, 16 but has been excluded as the prostate metastasis-suppressor gene within the vicinity of 17q21. 14,15 Since the human p75 NTR gene maps to the region of 17q21, 12 in the vicinity of a tumor-suppressor gene 13 and a metastasis-suppressor gene, 14,15 its function(s) within the human prostate may be of significance to the development of prostate cancer. In this context, the p75 NTR is able to induce apoptosis in a variety of cells 18,19 including TSU-pr1 human prostate tumor cells in vitro.…”

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Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

Krygier

Djakiew

2001

Intl Journal of Cancer

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The loss of tumor-and/or metastasis-suppressor gene function contributes to the transformation of human prostate epithelial cells to a malignant pathology. Such a putative tumor-suppressor and metastasis-suppressor gene(s) has been mapped to the region of 17q21, which coincidentally is in the vicinity of the human gene locus for the neurotrophin receptor p75 NTR . The p75 NTR is expressed in normal human prostate epithelial cells and exhibits an inverse association of p75 NTR expression with the malignant progression of the prostate, consistent with a pathologic role of the p75 NTR as a putative tumor and metastasis suppressor. Utilizing stable transfectants of the TSU-pr1 and PC-3 human prostate tumor cell lines that exhibit a rank order (dose-dependent) increase in p75 NTR protein expression, we investigated the effects of the p75 NTR in combination with its predominant ligand, nerve growth factor (NGF), on tumor cell growth. A rank order (dose-dependent) increase in p75 NTR expression was found to suppress the growth of prostate tumors in severe combined immunodeficient (SCID) mice. Treatment of these tumors with NGF stimulated both proliferation as indicated by PCNA expression and apoptosis as indicated by TUNEL assay, the net result of which was no change in the overall growth of the tumors. However, NGF was found to increase the formation of satellite tumors, both contiguous and noncontiguous with respect to the primary tumor mass, indicating dose-dependent induction of metastasis. Significantly, the formation of satellite tumors was suppressed by the expression of p75 NTR . This suggests that p75 NTR is a tumor suppressor of growth and a metastasis suppressor of NGF-stimulated migration of human prostate tumor cells.

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The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias.

Cited by 82 publications

References 36 publications

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

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

p75 Neurotrophin Receptor Inhibits Invasion and Metastasis of Gastric Cancer

Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

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The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias.

Cited by 82 publications

References 36 publications

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

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

p75 Neurotrophin Receptor Inhibits Invasion and Metastasis of Gastric Cancer

Neurotrophin receptor p75NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

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Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells