{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:22:47Z","timestamp":1761718967157,"version":"3.41.2"},"reference-count":49,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","award":["R21 CA238953"],"award-info":[{"award-number":["R21 CA238953"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Pancreatic cancer (PC) is acquired postnatally; to mimic this scenario, we developed an inducible KC (iKC) mouse model (KrasG12D;Ptf1a-CreERTM), in which Kras is activated at postnatally at week 16 upon tamoxifen administration. Upon TAM treatment, iKC mice develop PanIN lesions and PC with metastasis at 4 and 40th week, respectively, and exhibited acinar-to-ductal metaplasia (ADM) and transdifferentiation. Kras activation up-regulated the transcriptional factors Ncoa3, p-cJun, and FoxM, which in turn upregulated expression of transmembrane mucins (Muc1, Muc4, and Muc16) and secretory mucin (Muc5Ac). Interestingly, knock-down of KrasG12D in multiple PC cell lines resulted in down-regulation of MUC1, MUC4, MUC5AC, and MUC16. In addition, iKC mice exhibited ADM and transdifferentiation. Our results show the iKC mouse more closely mimics human PC development and can be used to investigate studies related to PDAC biomarkers, early onset of PDAC, and ADM. iKC model can also be used for pre-clinical strategies targeting mucin axis alone\/in combination with neo-adjuvant, immunotherapeutic approaches and to monitor chemotherapy response.<\/jats:p>","DOI":"10.1242\/bio.052878","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T15:57:51Z","timestamp":1595606271000},"source":"Crossref","is-referenced-by-count":8,"title":["Acinar transformed ductal cells exhibit differential mucin expression in a tamoxifen-induced pancreatic ductal adenocarcinoma mouse model"],"prefix":"10.1242","author":[{"given":"Kavita","family":"Mallya","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-6168","authenticated-orcid":false,"given":"Dhanya","family":"Haridas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2348-3901","authenticated-orcid":false,"given":"Parthasarathy","family":"Seshacharyulu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-2578","authenticated-orcid":false,"given":"Ramesh","family":"Pothuraju","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2649-3996","authenticated-orcid":false,"given":"Wade M.","family":"Junker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Sanguine Diagnostics and Therapeutics, Inc., Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-6671","authenticated-orcid":false,"given":"Shiv Ram","family":"Krishn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-7857","authenticated-orcid":false,"given":"Sakthivel","family":"Muniyan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-3048","authenticated-orcid":false,"given":"Raghupathy","family":"Vengoji","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9470-9317","authenticated-orcid":false,"given":"Surinder K.","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA"},{"name":"Eppley Institute for Research in Cancer & Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-8566","authenticated-orcid":false,"given":"Satyanarayana","family":"Rachagani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042700335672500_BIO052878C1","first-page":"4033","article-title":"Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance","volume":"7","author":"Andrianifahanana","year":"2001","journal-title":"Clin. 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