Tumour Biology of Gastroenteropancreatic Neuroendocrine Tumours

Neuroendocrine tumours of the gastroenteropancreatic tract (GEP NETs) represent a rare and heterogeneous group of tumours. Based on their ontogenetic origin, GEP NETs are classified into foregut, midgut and hindgut tumours. Although they have many features in common, their molecular backgrounds are obviously different. Elucidation of the key factors determining tumour biology has been hampered by the low incidence and high variability of these tumours in terms of origin, morphology and growth. However, recent years have shed some light on molecular genetics of these tumours, revealing important genetic factors as the RET proto-oncogene and the tumour suppressor menin as well as knowledge about the role of growth factors like IGF-1, TGF-β, VEGF and PDGF for the regulation of differentiation, growth and secretion. In the future, emerging molecular tools in rapid individual genome analysis and in proteomic and array technologies may help to delineate common patterns of NET disease.

[1]  M. Ichihara,et al.  RET and neuroendocrine tumors. , 2004, Cancer letters.

[2]  B. Boehm,et al.  Grap-2, a novel RET binding protein, is involved in RET mitogenic signaling , 2003, Oncogene.

[3]  B. Wiedenmann,et al.  Autocrine growth inhibition by transforming growth factor β-1 (TGFβ-1) in human neuroendocrine tumour cells , 2003 .

[4]  J. Reubi,et al.  Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[5]  B. Wiedenmann,et al.  Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. , 2003, Journal of the National Cancer Institute.

[6]  B. Wiedenmann,et al.  Autocrine growth inhibition by transforming growth factor beta-1 (TGFbeta-1) in human neuroendocrine tumour cells. , 2003, Gut.

[7]  M. Raffeld,et al.  Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  S. Schulz,et al.  Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies , 2002, Gut.

[9]  B. Simon,et al.  Tumor suppressor genes in the 9p21 gene cluster are selective targets of inactivation in neuroendocrine gastroenteropancreatic tumors. , 2001, Cancer research.

[10]  E. Szabo,et al.  Chromosome 18 deletions are common events in classical midgut carcinoid tumors , 2001, International journal of cancer.

[11]  A. Hoeflich,et al.  Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. , 2000, Cancer research.

[12]  R. Jensen,et al.  Carcinoid and pancreatic endocrine tumors: recent advances in molecular pathogenesis, localization, and treatment. , 2000, Current opinion in oncology.

[13]  V. Villanacci,et al.  Biological and Molecular Aspects of Gastroenteropancreatic Neuroendocrine Tumors , 2000, Digestion.

[14]  A. Calender.  Molecular Genetics of Neuroendocrine Tumors , 2000, Digestion.

[15]  M. Rothmund,et al.  Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors , 1999, Oncogene.

[16]  F. Collins,et al.  Menin Interacts with the AP1 Transcription Factor JunD and Represses JunD-Activated Transcription , 1999, Cell.

[17]  H. Fehmann,et al.  Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours , 1998, European journal of clinical investigation.

[18]  B. Wiedenmann,et al.  Molecular and cell biological aspects of neuroendocrine tumors of the gastroenteropancreatic system , 1998, Journal of Molecular Medicine.

[19]  C. Capella,et al.  Cell biology, clinicopathological profile, and classification of gastro-enteropancreatic endocrine tumors , 1998, Journal of Molecular Medicine.

[20]  J. Herman,et al.  Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: an analysis of p16/MTS1 tumor suppressor gene inactivation. , 1998, Cancer research.

[21]  I. Modlin,et al.  An analysis of 8305 cases of carcinoid tumors , 2000, Cancer.

[22]  G. Mengod,et al.  Somatostatin receptor subtypes sst1, sst2, sst3 and sst5expression in human pituitary, gastroentero‐pancreatic and mammary tumors , 1997 .

[23]  G. Mengod,et al.  Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. , 1997, International journal of cancer.

[24]  P. Neuhaus,et al.  Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. , 1996, Gut.

[25]  C. Heldin,et al.  Expression of transforming growth factors beta 1, beta 2, beta 3 in neuroendocrine tumors of the digestive system. , 1994, Anticancer research.

[26]  K. Öberg,et al.  Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system. , 1993, Acta oncologica.

[27]  C. Heldin,et al.  Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. , 1992, Cancer research.

[28]  B. Madewell,et al.  Neoplasms of endocrine glands. , 1977, The Veterinary clinics of North America.