PTPRM, a candidate tumor suppressor gene in small intestinal neuroendocrine tumors
2019 (English)In: Endocrine Connections, E-ISSN 2049-3614, Vol. 8, no 8, p. 1126-1135Article in journal (Refereed) Published
Abstract [en]
Small intestinal neuroendocrine tumors (SI-NETs) are small, slow growing neoplasms with loss of one copy of chromosome 18 as a common event. Frequently mutated genes on chromosome 18 or elsewhere have not been found so far. The aim of this study was to investigate a possible tumor suppressor role of the transmembrane receptor type tyrosine phosphatase PTP mu (PTPRM at 18p11) in SI-NETs. Immunohistochemistry, quantitative RT-PCR, colony formation assay and quantitative CpG methylation analysis by pyrosequencing were performed. Undetectable/very low levels of PTPRM or aberrant pattern of immunostaining, with both negative and positive areas, were detected in the majority of tumors (33/40), and a significantly reduced mRNA expression in metastases compared to primary tumors was observed. Both the DNA methylation inhibitor 5-aza-2'deoxycytidine and the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) induced PTPRM expression in CNDT2.5 and KRJ-I SI-NET cells. CpG methylation of upstream regulatory regions, the promoter region and the exon 1/intron 1 boundary was detected by pyrosequencing analysis of the two cell lines and not in the analyzed SI-NETs. Overexpression of PTPRM in the SI-NET cell lines reduced cell growth and cell proliferation and induced apoptosis. The tyrosine phosphatase activity of PTPRM was not involved in cell growth inhibition. The results support a role for PTPRM as a dysregulated candidate tumor suppressor gene in SI-NETs and further analyses of the involved mechanisms are warranted.
Place, publisher, year, edition, pages
BIOSCIENTIFICA LTD , 2019. Vol. 8, no 8, p. 1126-1135
Keywords [en]
DNA methylation, neuroendocrine tumors, epigenetic, SI-NETs, PTPRM
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-393899DOI: 10.1530/EC-19-0279ISI: 000483142900007PubMedID: 31349215OAI: oai:DiVA.org:uu-393899DiVA, id: diva2:1362314
Funder
Swedish Cancer SocietyErik, Karin och Gösta Selanders Foundation2019-10-182019-10-182023-08-28Bibliographically approved