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The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

Dupouy S, Viardot-Foucault V, Alifano M, Souazé F, Plu-Bureau G, Chaouat M, Lavaur A, Hugol D, Gespach C, Gompel A, Forgez P - PLoS ONE (2009)

Bottom Line: NTS is expressed and up-regulated by estrogen in normal epithelial breast cells.The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes.Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

View Article: PubMed Central - PubMed

Affiliation: INSERM-UPMC CDR Saint-Antoine EQ.5, Hôpital Saint-Antoine, Paris, France.

ABSTRACT

Background: The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion.

Methods and results: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients.

Conclusion: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

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Related in: MedlinePlus

Neurotensin expression in normal breast tissue.a) Left, one µg of total RNA from HBEC or whole gland were reverse-transcribed and a PCR experiment specific for NTS was performed. Right, one µg of total RNA from HBEC cells (control, treated with 10 nM estradiol (E2) with or without 1 µM ICI 182780) was reverse-transcribed. A PCR experiment was performed using specific primers for NTS and GAPDH. b) Normal duct exposed to NTS antibody at 1/500 dilution (1), after pre-incubation with the antigen peptide for 2 h at 10 nM (2), or without primary antibody (3), and lobule exposed to NTS antibody (4). Normal tissue exposed to NTS antibody at 1/500 dilution adjacent to tumor duct (5), lobule (6). The original magnification was 200×.
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pone-0004223-g001: Neurotensin expression in normal breast tissue.a) Left, one µg of total RNA from HBEC or whole gland were reverse-transcribed and a PCR experiment specific for NTS was performed. Right, one µg of total RNA from HBEC cells (control, treated with 10 nM estradiol (E2) with or without 1 µM ICI 182780) was reverse-transcribed. A PCR experiment was performed using specific primers for NTS and GAPDH. b) Normal duct exposed to NTS antibody at 1/500 dilution (1), after pre-incubation with the antigen peptide for 2 h at 10 nM (2), or without primary antibody (3), and lobule exposed to NTS antibody (4). Normal tissue exposed to NTS antibody at 1/500 dilution adjacent to tumor duct (5), lobule (6). The original magnification was 200×.

Mentions: The NTS gene was previously described as an estradiol target gene [16] with estradiol increasing NTS transcription in the preoptic area and neurosecretory cells of the hypothalamic arcuate nucleus [17], [18]. We hypothesized that NTS is also expressed in normal human breast tissue, and studied NTS transcript on normal mammary glands, and on eight different human breast epithelial cells (HBEC) cultures. We consistently detected NTS amplicon with low to medium intensity. Typical examples are shown in figure 1A left. In order to evaluate if NTS gene is also regulated by estradiol in human breast, HBEC were exposed to estradiol. As shown in figure 1A right, an enhancement of NTS transcripts was observed. This effect was abolished when ICI 182780, a pure anti-estrogen, was added concomitantly to estradiol (Figure 1A right) suggesting that estrogen receptors participate in the NTS gene regulation in human breast tissue. Corroborating these results, NTS expression was positively detected by immunohistochemistry in 19 (76%) biopsies of normal breast tissues from 25 premenopausal women. We observed NTS labeling within sparse epithelial cells of ducts and lobules (Figure 1B, 1 and 4). On the same slide we noticed that the lobular structures were labeled with a more intense staining than the duct structures. We also noticed that the normal adjacent tissue of invasive ductal breast carcinomas (IDCs) was very often labeled by NTS antibody, with similar intensity and cellular distribution as in the tissue from healthy women (Figure 1B, 5 and 6).


The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

Dupouy S, Viardot-Foucault V, Alifano M, Souazé F, Plu-Bureau G, Chaouat M, Lavaur A, Hugol D, Gespach C, Gompel A, Forgez P - PLoS ONE (2009)

Neurotensin expression in normal breast tissue.a) Left, one µg of total RNA from HBEC or whole gland were reverse-transcribed and a PCR experiment specific for NTS was performed. Right, one µg of total RNA from HBEC cells (control, treated with 10 nM estradiol (E2) with or without 1 µM ICI 182780) was reverse-transcribed. A PCR experiment was performed using specific primers for NTS and GAPDH. b) Normal duct exposed to NTS antibody at 1/500 dilution (1), after pre-incubation with the antigen peptide for 2 h at 10 nM (2), or without primary antibody (3), and lobule exposed to NTS antibody (4). Normal tissue exposed to NTS antibody at 1/500 dilution adjacent to tumor duct (5), lobule (6). The original magnification was 200×.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626627&req=5

pone-0004223-g001: Neurotensin expression in normal breast tissue.a) Left, one µg of total RNA from HBEC or whole gland were reverse-transcribed and a PCR experiment specific for NTS was performed. Right, one µg of total RNA from HBEC cells (control, treated with 10 nM estradiol (E2) with or without 1 µM ICI 182780) was reverse-transcribed. A PCR experiment was performed using specific primers for NTS and GAPDH. b) Normal duct exposed to NTS antibody at 1/500 dilution (1), after pre-incubation with the antigen peptide for 2 h at 10 nM (2), or without primary antibody (3), and lobule exposed to NTS antibody (4). Normal tissue exposed to NTS antibody at 1/500 dilution adjacent to tumor duct (5), lobule (6). The original magnification was 200×.
Mentions: The NTS gene was previously described as an estradiol target gene [16] with estradiol increasing NTS transcription in the preoptic area and neurosecretory cells of the hypothalamic arcuate nucleus [17], [18]. We hypothesized that NTS is also expressed in normal human breast tissue, and studied NTS transcript on normal mammary glands, and on eight different human breast epithelial cells (HBEC) cultures. We consistently detected NTS amplicon with low to medium intensity. Typical examples are shown in figure 1A left. In order to evaluate if NTS gene is also regulated by estradiol in human breast, HBEC were exposed to estradiol. As shown in figure 1A right, an enhancement of NTS transcripts was observed. This effect was abolished when ICI 182780, a pure anti-estrogen, was added concomitantly to estradiol (Figure 1A right) suggesting that estrogen receptors participate in the NTS gene regulation in human breast tissue. Corroborating these results, NTS expression was positively detected by immunohistochemistry in 19 (76%) biopsies of normal breast tissues from 25 premenopausal women. We observed NTS labeling within sparse epithelial cells of ducts and lobules (Figure 1B, 1 and 4). On the same slide we noticed that the lobular structures were labeled with a more intense staining than the duct structures. We also noticed that the normal adjacent tissue of invasive ductal breast carcinomas (IDCs) was very often labeled by NTS antibody, with similar intensity and cellular distribution as in the tissue from healthy women (Figure 1B, 5 and 6).

Bottom Line: NTS is expressed and up-regulated by estrogen in normal epithelial breast cells.The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes.Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

View Article: PubMed Central - PubMed

Affiliation: INSERM-UPMC CDR Saint-Antoine EQ.5, Hôpital Saint-Antoine, Paris, France.

ABSTRACT

Background: The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion.

Methods and results: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients.

Conclusion: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

Show MeSH
Related in: MedlinePlus