Abstract
IGFBP-2 (1) has been described as a brain tumor oncogene (2) and is widely expressed in cancers from different origins (3–8). IGFBP-2 alone cannot cause malignant transformation, yet progression of brain tumors to higher grade (9) and also has been provided as a protective element in earlier stages of multistage colon carcinogenesis (10). Therefore, it is crucial to understand the factors that determine expression patterns of IGFBP-2 under normal and malignant conditions. The present review provides a comprehensive update of known factors that have an impact on expression of IGFBP-2.
Highlights
After the identification of insulin-like growth factor (IGF) binding protein (IGFBP)-2 [1], it was realized that its expression both in liver and ovary is induced by E2 (Table 1) in hypophysectomized rats [11]
The present review provides a comprehensive update of known factors that have an impact on expression of IGFBP-2
In a wide variety of tissues, steroids have been identified as effectors of IGFBP-2 expression
Summary
After the identification of IGFBP-2 [1], it was realized that its expression both in liver and ovary is induced by E2 (Table 1) in hypophysectomized rats [11]. In human breast cancer cells (MCF-7), Mireuta and coworkers could demonstrate that the proximal promoter region of IGFBP-2 is activated by an IGF-I/PI3K/AKT/mTOR-dependent manner via an increase of nuclear Sp1 [44]. A positive effect of E2 on IGFBP-2 mRNA expression was present in MtT/S and GH3 cell lines established from rat pituitary adenomas [18]. DHEA increased IGF-I expression in the hypothalamus of rats but did not affect expression of IGFBP-2 [93].
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