title: Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.
abstract: The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting.
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kanaya
authors.affiliation: Department of Medical Oncology, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Department of Comparative Medicine, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Information Sciences, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kai
authors.affiliation: Department of Information Sciences, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Xueli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Shang Victoria
authors.initials: SV
authors.lastname: Wu
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Duc
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Nymph
authors.initials: N
authors.lastname: Chan
authors.affiliation: Department of Comparative Medicine, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Meng-Yin
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Clinical Trials Office, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Kirschenbaum
authors.affiliation: Department of Surgery, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Kruper
authors.affiliation: Department of Surgery, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Vito
authors.affiliation: Department of Surgery, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Behnam
authors.initials: B
authors.lastname: Badie
authors.affiliation: Department of Surgery, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Department of Medical Oncology, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Medical Oncology, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Arti
authors.initials: A
authors.lastname: Hurria
authors.affiliation: Department of Pathology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Chu
authors.initials: C
authors.lastname: Peiguo
authors.affiliation: Department of Medical Oncology, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mortimer
authors.affiliation: Department of Cancer Biology, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA. Electronic address: schen@coh.org.
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts / Q000378:metabolism* / Q000637:transplantation; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D059467:Transcriptome; D023041:Xenograft Model Antitumor Assays
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen
keywords: Breast cancer; ER+HER2+; ER+HER2−; Luminal A/B; Patient-derived tumor xenografts (PDXs)