ArticleThe American journal of pathology2009
Neuroendocrine cancer-specific up-regulating mechanism of insulin-like growth factor binding protein-2 in small cell lung cancer.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Rewiring the tumor microenvironment: IGFBP2 at the Nexus of remodeling and therapy resistance?Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Does subtyping of high-grade pulmonary neuroendocrine carcinomas have an impact on therapy selection?Translational lung cancer research · 2023Article
- Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour.International journal of molecular sciences · 2021Review
- Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance.International journal of molecular sciences · 2021Review
- Gene expression and prognosis of insulin‑like growth factor‑binding protein family members in non‑small cell lung cancer.Oncology reports · 2019Article
- IGFBP2 potentiates nuclear EGFR-STAT3 signaling.Oncogene · 2016Article
- IGFBP-2 - taking the lead in growth, metabolism and cancer.Journal of cell communication and signaling · 2015Article
- IGF-Binding Protein 2 - Oncogene or Tumor Suppressor?Frontiers in endocrinology · 2015Review
- Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer?Clinical & experimental metastasis · 2014Article
- Control of IGFBP-2 Expression by Steroids and Peptide Hormones in Vertebrates.Frontiers in endocrinology · 2014Review
- Early growth response-1 induces and enhances vascular endothelial growth factor-A expression in lung cancer cells.The American journal of pathology · 2010Article
- Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma: IGF-independent antiapoptotic effect via caspase-3.The American journal of pathology · 2010Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small cell lung cancer (SCLC) exhibits insulin-like growth factor-dependent growth. SCLC is the most aggressive among known in vivo lung cancers, whereas in vitro growth of SCLC is paradoxically slow as compared with that of non-SCLC (NSCLC). In this study, we demonstrate that SCLC cells overexpress insulin-like growth factor binding protein (IGFBP)-2 via NeuroD, a neuroendocrine cell-specific transcription factor. Chromatin immunoprecipitation, electrophoretic mobility shift, and IGFBP-2 promoter assays all revealed that NeuroD binds to the E-box in the 5'-untranslated region of IGFBP-2. A NeuroD transgene in both airway epithelial and NSCLC cells up-regulated the transcription of IGFBP-2 and retarded cell growth. Recombinant IGFBP-2 repressed the growth of both airway epithelial and NSCLC cells in a dose-dependent manner. A NeuroD-specific small interfering RNA repressed IGFBP-2 expression in SCLC, and neutralization of IGFBP-2 and an IGFBP-2-specific small interfering RNA increased SCLC cell growth. Pathological samples of SCLC also expressed IGFBP-2 abundantly, as compared with NSCLC, and showed only rare (8%) IGFBP-2 promoter methylation, whereas the IGFBP-2 promoter was methylated in 71% of adenocarcinomas and 29% of squamous cell carcinomas. These findings suggest that 1) SCLC has an IGFBP-2 overexpression mechanism distinct from NSCLC, 2) secreted IGFBP-2 contributes to the slow growth of SCLC in vitro, and 3) the epigenetic alterations in the IGFBP-2 promoter contribute to the striking differences in IGFBP-2 expression between SCLC and NSCLC in vivo.
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