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IGFBP7: an oncosuppressor gene in thyroid carcinogenesis
M G Vizioli1, M Sensi, C Miranda
1Molecular Mechanisms Unit, Department of Experimental Oncology and Molecular Medicine, IRCCS Foundation--Istituto Nazionale dei Tumori, Milan, Italy.
Oncogene
|May 5, 2010
Summary
Loss of Insulin-like growth factor-binding protein 7 (IGFBP7) expression is linked to thyroid cancer development. Restoring IGFBP7 levels inhibits tumor growth and migration, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein regulating cell proliferation, senescence, and apoptosis.
- Loss of IGFBP7 expression is implicated in various human cancers, including melanoma and colon cancer.
- Thyroid tumors exhibit altered gene expression patterns, necessitating investigation into specific molecular players.
Purpose of the Study:
- To investigate the role of IGFBP7 in thyroid carcinogenesis.
- To determine if IGFBP7 downregulation is a feature of thyroid tumors.
- To explore the functional consequences of IGFBP7 loss in thyroid cancer cells.
Main Methods:
- Microarray gene expression analysis of thyroid tumors and normal tissue.
- Bioinformatic evaluation of publicly available thyroid papillary cancer (PTC) datasets.
- Functional studies using the PTC-derived NIM1 cell line with repressed IGFBP7 expression.
- Assessment of cell proliferation, migration, anchorage-independent growth, and tumorigenicity.
- Investigation of apoptosis induction by IGFBP7.
Main Results:
- IGFBP7 gene expression was found to be downregulated in follicular and papillary thyroid tumors compared to normal thyroid tissue.
- Publicly available datasets confirmed consistent downregulation of IGFBP7 transcript levels in a fraction of PTCs.
- In the NIM1 cell line, repressed IGFBP7 expression due to promoter hypermethylation was observed.
- Reintroducing IGFBP7 protein or expression reduced cell growth rate, migration, anchorage-independent growth, and tumorigenicity.
- The anti-tumor effects of IGFBP7 were linked to the induction of apoptosis.
Conclusions:
- Loss of IGFBP7 expression plays a functional role in thyroid carcinogenesis.
- IGFBP7 downregulation is a significant event in thyroid tumor development.
- Restoration of IGFBP7 function presents a potential therapeutic strategy for thyroid cancer.
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