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.