title: Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice.
abstract: Estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF-1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor-bearing mice were divided into seven groups: 17β-estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF-1, IGF-1+AG1024 (IGF-1 inhibitor), E2+IGF-1, E2+IGF-1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERβ, IGF-1, IGF-1R and Ki67 was examined using tissue-microarray-immunohistochemistry, and IGF-1, p-ERβ, p-IGF-1R, p-MAPK and p-AKT levels were determined based on Western blot analysis. Fluorescence-quantitative polymerase chain reaction was used to detect the mRNA expression of ERβ, ERβ2 and IGF-1R. Tumors were found in 93.88% (46/49) of urethane-treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF-1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF-1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERβ, p-ERβ, ERβ2, IGF-1, IGF-1R, p-IGF-1R, p-MAPK, p-AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF-1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERβ1, ERβ2 and IGF-1R play important roles.
authors: Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Hexiao
authors: H
authors: Tang
authors: Yongde
authors: Y
authors: Liao
authors: Liqiang
authors: L
authors: Xu
authors: Chao
authors: C
authors: Zhang
authors: Zhaoguo
authors: Z
authors: Liu
authors: Yu
authors: Y
authors: Deng
authors: Zhixiao
authors: Z
authors: Jiang
authors: Shengling
authors: S
authors: Fu
authors: Zhenguang
authors: Z
authors: Chen
authors: Sheng
authors: S
authors: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004967:Estrogens; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Western blot analysis; estrogen receptor β; insulin-like growth factor-1 receptor; lung adenocarcinoma; mouse lung cancer model; real-time fluorescence-quantitative PCR; tissue microarray-immunohistochemistry