Endocrine Gene Neurotensin: Molecular Mechanisms and a Model of Intestinal Differentiation

Evers, B. Mark

doi:10.1007/s00268-002-4055-3

Cited by 27 publications

(18 citation statements)

References 43 publications

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“…Evidence shows that neurotensin gene hypomethylation (41), along with the activation of transcription factors activator protein-1 (AP-1) and cAMP-responsive element-binding protein and the oncogenic signaling factors RAS and Src, are potential mechanisms leading to neurotensin overexpression and secretion during cancer progression (42). It is noteworthy that estrogens can also activate neurotensin expression in the brain through the cAMP cascade and through an additional, nonconventional, steroid receptor pathway (43).…”

Section: Discussionmentioning

confidence: 99%

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

et al. 2006

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Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the highaffinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients. (Cancer Res 2006; 66(12): 6243-9)

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Section: Discussionmentioning

confidence: 99%

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

et al. 2006

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“…This is different from the results obtained in morphological and histological observations. Neurotensin is a tridecapeptide, which stimulates pancreatic and biliary secretion, and colonic motility, and inhibits small bowel and gastric motility (Evers 2002). In rat, neurotensin mRNA is restricted in the small intestine, with the highest expression in the jejunoileal section (Carraway & Leeman 1976).…”

Section: Discussionmentioning

confidence: 99%

Division of Chinese soft‐shelled turtle intestine with molecular markers is slightly different from the morphological and histological observation

Zhang

Song

Xiao

et al. 2018

Integrative Zoology

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The Chinese soft-shelled turtle (Pelodiscus sinensis) is a commercially important species in Asian countries. Knowledge of its nutritional requirements and physiology is essential for determining the appropriate content of the feed for this animal. However, the lack of functional characterization of the intestine of this turtle limits the understanding of its absorption and utilization of nutritional materials. To solve this problem, this work utilized anatomical and histological methods to characterize 9 segments sampled along the anterior-posterior axis of the intestine. Furthermore, 9 genes, which have been well documented in the intestine division of mammals and fish, were employed to functionally characterize the 9 sampled segments. Our results suggest that regions covering from the starting site to S3 (position at 29.9% of the total length from the starting of the intestine) are the equivalent of mammalian dedumonen, and those covering S4 (40.2%) and S5 (65.4%), posterior to S8 (92.7%), are the equivalent of the mammalian ileum and the large intestine, respectively. As to the region spaning S6 (81.3%) and S7 (87.3%), its functional equivalent (small intestine or large intestine) may be variable and depends on the functional genes. This molecular characterization in relation to the division of the intestine of Chinese soft-shelled turtle may contribute to the understanding of the nutritional physiology of the turtle, and promote Chinese soft-shelled turtle production.

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“…The gut peptide neurotensin (NT), 1 a tridecapeptide localized to enteroendocrine cells (N cells) of the distal small bowel (2,3), facilitates fatty acid translocation (4), affects gut motility (5), and stimulates growth of normal gut mucosa (6,7). In addition to its trophic effects on normal GI tissues, NT stimulates proliferation of certain pancreatic, colonic, and prostatic cancers bearing NT receptors (NTR) (8).…”

mentioning

confidence: 99%

The Role of Protein Kinase D in Neurotensin Secretion Mediated by Protein Kinase C-α/-δ and Rho/Rho Kinase

O’Connor

Hellmich

et al. 2004

Journal of Biological Chemistry

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Neurotensin (NT) is a gut peptide that plays an important role in gastrointestinal (GI) secretion, motility, and growth as well as the proliferation of NT receptor positive cancers. Secretion of NT is regulated by phorbol ester-sensitive protein kinase C (PKC) isoforms-␣ and -␦ and may involve protein kinase D (PKD). The purpose of our present study was: (i) to define the role of PKD in NT release from BON endocrine cells and (ii) to delineate the upstream signaling mechanisms mediating this effect. Here, we demonstrate that small interfering RNA (siRNA) targeted against PKD dramatically inhibited both basal and PMA-stimulated NT secretion; NT release is significantly increased by overexpression of PKD. PKC-␣ and -␦ siRNA attenuated PKD activity, whereas overexpression of PKC-␣ and -␦ enhanced PKD activity. Rho kinase (ROK) siRNA significantly inhibited NT secretion, whereas overexpression of ROK␣ effectively increased NT release. Rho protein inhibitor C3 dramatically inhibited both NT secretion and PKD activity. In conclusion, our results demonstrate that PKD activation plays a central role in NT peptide secretion; upstream regulators of PKD include PKC-␣ and -␦ and Rho/ROK. Importantly, our results identify novel signaling pathways, which culminate in gut peptide release.Regulatory hormones, localized to specialized endocrine cells in the small bowel, control numerous physiological functions of the gastrointestinal (GI) tract including secretion, motility, and mucosal growth (1). The gut peptide neurotensin (NT), 1 a tridecapeptide localized to enteroendocrine cells (N cells) of the distal small bowel (2, 3), facilitates fatty acid translocation (4), affects gut motility (5), and stimulates growth of normal gut mucosa (6, 7). In addition to its trophic effects on normal GI tissues, NT stimulates proliferation of certain pancreatic, colonic, and prostatic cancers bearing NT receptors (NTR) (8). Although the mechanisms for pancreatic hormone release have been well characterized (9), the signal transduction pathways regulating stimuli-induced gut hormone secretion are not entirely understood. One reason for this paucity in our understanding is the relative lack of useful in vitro models that recapitulate in vivo properties of intestinal endocrine cells.The BON endocrine cell line was established from a human pancreatic carcinoid tumor and characterized in our laboratory (10). These cells have served as an invaluable in vitro model for hormone secretion studies. Similar to the terminally differentiated N cell of the small bowel, BON cells express high levels of NT/neuromedin N mRNA, synthesize and secrete NT peptide, and process the NT/neuromedin N precursor protein in a fashion identical to that of the normal intestine (11). BON cells exhibit morphological and biochemical characteristics consistent with the enteroendocrine cell phenotype, including the presence of numerous dense core granules and the expression and secretion of chromogranin A and other peptides (e.g. pancreastatin) (10, 12, 13). Thus, the BON cel...

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Endocrine Gene Neurotensin: Molecular Mechanisms and a Model of Intestinal Differentiation

Cited by 27 publications

References 43 publications

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

Expression of Neurotensin and NT1 Receptor in Human Breast Cancer: A Potential Role in Tumor Progression

Division of Chinese soft‐shelled turtle intestine with molecular markers is slightly different from the morphological and histological observation

The Role of Protein Kinase D in Neurotensin Secretion Mediated by Protein Kinase C-α/-δ and Rho/Rho Kinase

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