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Abstract

The insulin-like growth factors are mitogens and survival factors for normal mammary epithelial cells in vitro. Data reviewed here demonstrate that mRNAs for IGF-I and IGF-II, the IGF type I receptor and the IGFBPs are expressed locally in mammary tissue during pubertal and pregnancy-induced growth and differentiation of murine mammary glands. IGF-I, IGF-II and the IGF-IR were expressed in terminal end buds (TEBs) in virgin glands during ductal growth. In addition, IGF-II and IGF-IR mRNAs were expressed in ductal and alveolar epithelium in glands throughout postnatal development. Consistent with these results, IGF-I promoted ductal growth and proliferation in mouse mammary glands in organ culture. In addition to endogenous expression of the IGFs and IGF-IR, the IGFBPs showed a varied pattern of expression in mammary tissue during postnatal development. For example, IGFBP-3 and -5 mRNAs were expressed in TEBs and ducts while IGFBP-2 and -4 mRNAs were expressed in stromal cells immediately surrounding the epithelium. These results support a role for the IGFs and IGFBPs as local mediators of postnatal mammary gland growth and differentiation.

Obesity Alters Gene Expression for GH/IGF-I Axis in Mouse Mammary Fat Pads: Differential Role of Cortistatin and Somatostatin

“…Specifically, IGF-I, IGF-IR, GH-R and PRL-R (which shares a common ancestor with GH-R due to gene duplication) [ 53 ] are expressed at high levels in mouse MFPs, while GH (and PRL) expression is barely detectable, at least in mature female mice. These data are consistent with previous studies [ 4 ] and reinforce the idea that circulating, rather than locally produced GH acts on MFPs through GH-R to stimulate IGF-I production, which, in turn, can be acting in an autocrine or paracrine fashion to regulate mammary gland development [ 3 , 10 – 14 , 54 , 55 ]. In fact, locally produced IGF-I has been shown to be necessary for mammary gland development [ 3 , 10 – 14 ] and could be involved in the progression of mammary gland malignancies [ 10 ].…”

Pilot and feasibility study: prospective proteomic profiling of mammary epithelial cells from high-risk women provides evidence of activation of pro-survival pathways

“…For example, the superfamily of receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR or related ErbB family) and insulin-like growth factor receptor (IGF-1R), has proliferative and survival roles during mammary ductal outgrowth and branching [1, 2]. However, overexpression of these RTKs can disrupt the development and lead to tumorigenesis [3, 4]. In addition, the superfamily of serine/threonine kinases, such as Protein Kinase B/Akt, plays an important role in mammary carcinogenesis.…”

LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is predictive for tumor cell spread and overall survival

“…Microsatellite marker D6S1581 is located at 6q25.1, 25 kb proximal to the mannose 6-phosphate/insulin-like growth factor II receptor ( M6P/IGF2R ) locus [36]. This receptor is well described in breast cancer [37-39] and is supposed to act as a tumor suppressor gene by negatively regulating cell survival, tumor invasion and metastasis [40]. Moreover, LOH at M6P/IGF2R is well known to be a frequent event in primary ovarian cancers [41] and a low D6S1581 copy number was associated with platinum-resistant condition in ovarian cancer [36].…”