PMID- 30460471 OWN - NLM STAT- MEDLINE DCOM- 20200305 LR - 20200305 IS - 1869-1889 (Electronic) IS - 1674-7305 (Linking) VI - 62 IP - 2 DP - 2019 Feb TI - Integrin-interacting protein Kindlin-2 induces mammary tumors in transgenic mice. PG - 225-234 LID - 10.1007/s11427-018-9336-6 [doi] AB - Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus (MMTV) long terminal repeat (LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and beta-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway. FAU - Li, Bing AU - Li B AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Chi, Xiaochun AU - Chi X AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Song, Jiagui AU - Song J AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Tang, Yan AU - Tang Y AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Du, Juan AU - Du J AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - He, Xiaokun AU - He X AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Sun, Xiaoran AU - Sun X AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Bi, Zhenwu AU - Bi Z AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. FAU - Wang, Yunling AU - Wang Y AD - Institute of Cardiovascular Research, Peking University Health Science Center, Beijing, 100191, China. FAU - Zhan, Jun AU - Zhan J AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. Zhanjun@bjmu.edu.cn. FAU - Zhang, Hongquan AU - Zhang H AD - Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China. Hongquan.Zhang@bjmu.edu.cn. LA - eng PT - Journal Article DEP - 20181119 PL - China TA - Sci China Life Sci JT - Science China. Life sciences JID - 101529880 RN - 0 (CTNNB1 protein, mouse) RN - 0 (Cytoskeletal Proteins) RN - 0 (Muscle Proteins) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - 0 (beta Catenin) RN - 0 (kindlin-2 protein, mouse) RN - EC 2.7.10.1 (Erbb2 protein, mouse) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Animals MH - Carcinogenesis/genetics/metabolism/pathology MH - Cell Differentiation MH - Cell Proliferation MH - Cytoskeletal Proteins/genetics/*metabolism MH - Epithelial Cells/metabolism/pathology MH - Female MH - Gene Expression MH - Mammary Glands, Animal/metabolism/pathology MH - Mammary Neoplasms, Animal/*genetics/metabolism/pathology MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Mice, Transgenic MH - Muscle Proteins/genetics/*metabolism MH - Pregnancy MH - Promoter Regions, Genetic MH - Receptor, ErbB-2/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - *Wnt Signaling Pathway MH - beta Catenin/*metabolism OTO - NOTNLM OT - Kindlin-2 OT - breast cancer OT - mammary tumorigenesis OT - mouse mammary gland growth OT - transgenic mouse EDAT- 2018/11/22 06:00 MHDA- 2020/03/07 06:00 CRDT- 2018/11/22 06:00 PHST- 2018/06/30 00:00 [received] PHST- 2018/07/23 00:00 [accepted] PHST- 2018/11/22 06:00 [pubmed] PHST- 2020/03/07 06:00 [medline] PHST- 2018/11/22 06:00 [entrez] AID - 10.1007/s11427-018-9336-6 [pii] AID - 10.1007/s11427-018-9336-6 [doi] PST - ppublish SO - Sci China Life Sci. 2019 Feb;62(2):225-234. doi: 10.1007/s11427-018-9336-6. Epub 2018 Nov 19.