{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:48:28Z","timestamp":1782236908823,"version":"3.54.5"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:00:00Z","timestamp":1440547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"RHA; The Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (NTNU)","award":["46055600-68"],"award-info":[{"award-number":["46055600-68"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The oxyntic proliferative isthmus zone contains the main stem\/progenitor cells that provide for physiological renewal of the distinct mature cell lineages in the oxyntic epithelium of the stomach. These cells are also proposed to be the potential cells\u2010of\u2010origin of gastric cancer, although little is known about their molecular characteristics and specific biological markers are lacking. In this study, we developed a method for serial section\u2010navigated laser microdissection to isolate cells from the proliferative isthmus zone of rat gastric oxyntic mucosa for genome\u2010wide microarray gene expression analysis. Enrichment analysis showed a distinct gene expression profile for the isthmus zone, with genes regulating intracellular processes such as the cell cycle and ribosomal activity. The profile was also related to stem cell transcriptional networks and stomach neoplasia. Genes expressed uniquely in the isthmus zone were associated with <jats:styled-content style=\"fixed-case\">E2F<\/jats:styled-content> transcription factor 1 (<jats:styled-content style=\"fixed-case\">E2F1<\/jats:styled-content>), which participates in the self\u2010renewal of stem cells and in gastric carcinogenesis. One of the unique genes was <jats:italic>Aspm<\/jats:italic> [Asp (abnormal spindle) homologue, microcephaly\u2010associated (<jats:italic>Drosophila<\/jats:italic>)]. Here we show <jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content> in single scattered epithelial cells located in the proliferative isthmus zone of rat, mouse and human oxyntic mucosa, which do not seem to be actively dividing. The <jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content>\u2010expressing cells are mainly mature cell marker\u2010deficient, except for a limited overlap with cells with neuroendocrine and tuft cell features. Further, both <jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">E2F1<\/jats:styled-content> were expressed in human gastric cancer cell lines and increased and correlated in human gastric adenocarcinomas compared to non\u2010tumour mucosa, as shown by expression profile analyses and immunohistochemistry. The association between <jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content> and the transcription factor <jats:styled-content style=\"fixed-case\">E2F1<\/jats:styled-content> in gastric tissue is relevant, due to their common involvement in crucial cell fate\u2010regulatory mechanisms. Our results thus introduce <jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content> as a novel possible oxyntic stem\/progenitor cell marker that may be involved in both normal gastric physiology and gastric carcinogenesis. \u00a9 2015 Authors. <jats:italic>Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4591","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T04:51:30Z","timestamp":1437022290000},"page":"447-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Genome\u2010wide analysis of the oxyntic proliferative isthmus zone reveals <scp>ASPM<\/scp> as a possible gastric stem\/progenitor cell marker over\u2010expressed in cancer"],"prefix":"10.1002","volume":"237","author":[{"given":"P\u00e5l","family":"Vange","sequence":"first","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Norwegian University of Science and Technology (NTNU)  Trondheim Norway"},{"name":"Central Norway Regional Health Authority (RHA)  Stj\u00f8rdal Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torunn","family":"Bruland","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Norwegian University of Science and Technology (NTNU)  Trondheim Norway"},{"name":"Central Norway Regional Health Authority (RHA)  Stj\u00f8rdal Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidar","family":"Beisvag","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Norwegian University of Science and Technology (NTNU)  Trondheim 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