Overexpression of the Sm-like proto-oncogene in primary and metastatic pancreatic endocrine tumors.

CONTEXT The cancer associated Sm-like proto-oncogene mRNA has been found to be overexpressed in the majority of pancreatic adenocarcinomas and is necessary for the transformed phenotype in pancreatic cancer cell lines. However, expression levels have not been examined in other types of pancreatic neoplasms, such as pancreatic endocrine tumors. SETTING Fifteen primary pancreatic endocrine tumors, including five insulinomas and 10 non-functioning tumors, along with seven hepatic metastatic pancreatic endocrine tumors. MAIN OUTCOME MEASURES Quantitative expression levels of cancer associated Sm-like mRNA were measured by real-time PCR. Overexpression was defined as a two-fold or greater value when compared to the expression levels found in normal pancreatic islet cells obtained from healthy donors. RESULTS In primary tumors, four of the 10 non-functioning pancreatic endocrine tumors were found to overexpress cancer associated Sm-like mRNA (40%). Three of the five (60%) insulinomas also overexpressed cancer associated Sm-like mRNA. In total, cancer associated Sm-like mRNA was overexpressed in seven of 15 primary tumors (47%) and in the majority (71%, 5 of 7) of the hepatic metastases. CONCLUSIONS Our results indicate that the cancer associated Sm-like mRNA gene may also play a role in the tumorigenesis of pancreatic endocrine tumors.

[1]  Jun Octreotide , 1989, The Lancet.

[2]  A. Scarpa,et al.  Role of disease‐causing genes in sporadic pancreatic endocrine tumors: MEN1 andVHL , 2001, Genes, chromosomes & cancer.

[3]  A. Scarpa,et al.  Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis , 2001, British Journal of Cancer.

[4]  D. Watson,et al.  The cancer-associated Sm-like oncogene: a novel target for the gene therapy of pancreatic cancer. , 2000, Surgery.

[5]  H. Röher,et al.  Lack of MEN1 gene mutations in 27 sporadic insulinomas , 2000, European journal of clinical investigation.

[6]  E. Speel,et al.  Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. , 1999, The American journal of pathology.

[7]  M. Sawicki,et al.  Mutation of the MENIN gene in sporadic pancreatic endocrine tumors. , 1998, Cancer research.

[8]  G. Pelosi,et al.  Pancreatic endocrine tumours: evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p , 1998, The Journal of pathology.

[9]  T. Yokoi,et al.  Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[10]  J. Rastad,et al.  Mutation of the multiple endocrine neoplasia type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas. , 1998, Cancer research.

[11]  F. Collins,et al.  Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. , 1997, Cancer research.

[12]  D. Watson,et al.  CaSm: an Sm-like protein that contributes to the transformed state in cancer cells. , 1997, Cancer research.

[13]  B. Séraphin Sm and Sm‐like proteins belong to a large family: identification of proteins of the U6 as well as the U1, U2, U4 and U5 snRNPs. , 1995, The EMBO journal.

[14]  R. Lührmann,et al.  snRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in Sm protein‐protein interactions. , 1995, The EMBO journal.

[15]  N. Pellegata,et al.  K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. , 1994, Cancer research.

[16]  L. Villani,et al.  Classification and histogenesis of gastroenteropancreatic endocrine tumours , 1990, European journal of clinical investigation.

[17]  A. Scarpa,et al.  High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications. , 2001, Cancer research.

[18]  A. Scarpa,et al.  Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q. , 2001, The American journal of pathology.