{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:39:49Z","timestamp":1747147189970,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with human epidermal growth factor receptor 2 (HER2)\u2010positive breast cancer who fail to respond to anti\u2010HER2 treatments have poor prognoses. Most trastuzumab\u2010resistant breast cancer cell lines available from biobanks feature either <jats:italic>phosphoinositide\u20103\u2010kinase<\/jats:italic>, <jats:italic>catalytic<\/jats:italic>, <jats:italic>alpha<\/jats:italic> (<jats:italic>PIK3CA<\/jats:italic>) mutation or the loss of phosphatase and tensin homolog (PTEN). However, <jats:italic>PIK3CA<\/jats:italic> mutations and\/or PTEN loss do not account for most trastuzumab\u2010resistant tumors in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Breast cancer cells were collected from one patient's malignant ascites. These cells were cultured and maintained to develop a stable cell line, which we named CK\u2010MB\u20101. We used western blotting to evaluate protein expression. The <jats:italic>PIK3CA<\/jats:italic> status of CK\u2010MB\u20101 cells was analyzed using Sanger sequencing and validated using next\u2010generation sequencing. In vivo, CK\u2010MB\u20101 xenograft tumor models were developed in zebrafish and immunodeficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CK\u2010MB\u20101 cells maintained the major characteristics of the parental tumor including HER2 positivity and estrogen receptor negativity. The HER2 gene amplification of CK\u2010MB\u20101 cells was detected by fluorescence in situ hybridization. The integrity of PTEN was confirmed by its positive protein expression and the absence of gene mutations. No common <jats:italic>PIK3CA<\/jats:italic> mutation was detected. Compared with the findings in two other HER2\u2010positive trastuzumab\u2010resistant cell lines, CK\u2010MB\u20101 cells exhibited greater resistance to trastuzumab, chemotherapeutics, and small\u2010molecule drugs. Trastuzumab resistance in CK\u2010MB\u20101 cells was confirmed in vivo using the NOD SCID mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CK\u2010MB\u20101 cells represent a stable HER2\u2010positive trastuzumab\u2010resistant breast cancer cell line. The resistance of CK\u2010MB\u20101 cells does not originate from the PTEN or phosphoinositide 3\u2010kinase signaling pathway, which can provide an alternative approach for potential drugs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3824","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T09:05:47Z","timestamp":1614935147000},"page":"2370-2379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of the CK\u2010MB\u20101 trastuzumab\u2010resistant HER2\u2010positive breast cancer cell line and xenograft animal models"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8485-270X","authenticated-orcid":false,"given":"Wei\u2010Pang","family":"Chung","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Oncology National Cheng Kung 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