Prognostic Significance of Insulin-like Growth Factor-Binding Protein Expression in Axillary Lymph Node-Negative Breast Cancer

Yee, Douglas; Sharma, Jivesh; Hilsenbeck, Susan G.

doi:10.1093/jnci/86.23.1785

Cited by 38 publications

(22 citation statements)

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“…Since IGF-BP4, -BP5 and -BP2 have been shown to be positively involved in controlling cellular proliferation , the retinoid-induced cell growth inhibition may also be related to the observed decrease in their secretion. Indeed, in a recent study, low IGF-BP4 was correlated with improved survival in women with large tumour size (Yee et al, 1994). Secretion of IGF-BPl was evident only in MDA-MB231, as previously described (Yee et al, 1991).…”

Section: Discussionsupporting

confidence: 61%

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines

Favoni¹,

Cupis²,

Bruno³

et al. 1998

Br J Cancer

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Section: Discussionsupporting

confidence: 61%

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines

Favoni¹,

Cupis²,

Bruno³

et al. 1998

Br J Cancer

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“…Despite that, the prognostic role of IGFBP3 itself remains elusive. This reflects the complexity of biological IGFBP3 activity in tumor cells (10,(30)(31)(32)(33) and possibly the fact that IGFBP3, due to its expression in endothelial cells, is increased in highly vascular tumors (34,35). Furthermore, the IGFBP3 concentration in tumor tissue depends on the patients' attributes.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on IGFBP2 expression in breast tumor tissue are still limited in number. The reports regarding the correlation between IGFBP2 and ER expression are contradictory (9)(10)(11)(12). Few studies investigated the prognostic effect of IGFBP2.…”

Section: Discussionmentioning

confidence: 99%

“…Much less is known about the prognostic relevance of autocrine and paracrine IGF signaling in tumor tissue. Several breast cancer studies reported on the correlation between estrogen receptor (ER) status and the expression patterns of IGF-related proteins (9)(10)(11)(12), but only few also evaluated the effect of IGF-related mRNA or protein expressions in tumor tissue on survival (9,(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

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IGFBP2 and IGFBP3 Protein Expressions in Human Breast Cancer: Association with Hormonal Factors and Obesity

Probst‐Hensch

Steiner

Schraml

et al. 2010

Clinical Cancer Research

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Purpose: The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics.Experimental Design: IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, HER2 gene amplification, menopausal status, body mass index, and survival with IGF protein expression.Results: In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; P = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival.Conclusions: According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight. Clin Cancer Res; 16(3); 1025-32. ©2010 AACR.Understanding the biology of breast cancer progression is an important aspect of identifying therapeutic targets. Both obesity at diagnosis and subsequent weight gain are predictive of worse breast cancer survival (1). The obesity-breast cancer association may in part be related to hyperinsulinemia, the concomitant decrease in insulin-like growth factor (IGF)-binding proteins (IGFBP)1 and IGFBP2, and the resulting increase in bioactive IGFI (2). IGFI and IGF2 play a role in mammary gland development (3-5). They have mitogenic, antiapoptotic, and proangiogenic effects and stimulate the motility of breast cancer cells in vitro (3). The two growth factors act through IGFI receptor (IGFIR) homodimerization (3). Their bioavailability in circulation and tissues is regulated by at least six IGF-binding proteins. IGFBP3 and IGFBP2 are the most abundant IGFBPs in the blood. In addition to regulating IGF activity, IGFBPs exert additional IGF-independent effects (6).Transgenic mice deficient in IGFI exhibit a decreased susceptibility to mammary carcinogens (7). Tumor incidence is increased in mice expressing IGFI or IGF2 in the mammary gland (3). According to several meta-analyses and systematic reviews, circulating concentrations of IGFI and less consistently of IGFBP3 were positively associated with premenopausal breast cancer (8). Much less is known about the prognostic relevance of autocrine and paracrine IGF signaling in tumor tissue. Several breast cancer studies reported on the correlation between estrogen receptor (ER) status and the expression patterns of IGF-related proteins (9-12...

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“…IGFBP-5 is expressed in breast cancer tissue (24) and cell lines (25) and is positively correlated with estrogen receptor status. Because of the contradictory data on the role of IGFBP-5 in cancer cell growth, we directly examined the effect of stable expression of IGFBP-5 on the growth of human breast cancer cells in vitro and in vivo.…”

mentioning

confidence: 99%

Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo

Butt

Dickson

McDougall

et al. 2003

Journal of Biological Chemistry

131

123

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The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear. We determined the effects of IGFBP-5 expression on the growth of human breast cancer cell lines in vivo and in vitro. Expression of IGFBP-5, both by stable transfection and adenoviral-mediated infection, was inhibitory to the growth of MDA-MB-231 and Hs578T human breast cancer cells over a 13-day period. IGFBP-5 expression resulted in a G 2 /M cell cycle arrest and the induction of apoptosis in both cell lines, an effect that was abrogated in the presence of the broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced apoptosis was associated with a transcriptional increase in expression of the proapoptotic regulator bax and decrease in the anti-apoptotic bcl-2 compared with vector controls. Secreted IGFBP-5 when added exogenously to breast cancer cells was not internalized and had no effect on cell growth or apoptosis, suggesting that IGFBP-5 may elicit its inhibitory effects via a novel, intracrine mechanism. In athymic nude mice, stable expression of IGFBP-5 significantly inhibited both the formation and growth of tumors derived from MDA-MB-231 cells. IGFBP-5-expressing tumors also had a significantly elevated level of bax mRNA and decreased levels of bcl-2 mRNA compared with vector tumors. These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators.The insulin-like growth factor-binding proteins (IGFBPs) 1 are a family of proteins that bind with high affinity to IGFs and modulate their mitogenic actions by regulating their ability to interact with their signaling receptor, the type I IGF receptor (IGFRI, reviewed in Ref. 1). However, it is now becoming clear that many IGFBPs have direct roles in the regulation of cell growth and cell death. For example, we and others have demonstrated the antiproliferative and proapoptotic effects of IGFBP-3 in breast (2-4) and prostate (4) cancer cell lines.The role of IGFBP-5 in cell growth is complex, with reports that it can either stimulate or inhibit cell proliferation in various experimental systems (5-7). There is also evidence that IGFBP-5 expression is up-regulated by antiproliferative agents such as retinoic acid (8), vitamin D-related compounds (9), and antiestrogen ICI 182780 (10), with some evidence that it may mediate their growth inhibitory effects (8, 10). Similarly, growth stimulation of human breast cancer cells by estradiol is associated with a down-regulation of IGFBP-5 expression (10), although exogenous IGFBP-5 had no effect on IGF-I-stimulated DNA synthesis in the breast cancer cell line, MCF-7 (11). They demonstrated that addition of exogenous IGFBP-5 to Hs578T cells protects these cells from ceramide-induced apoptosis, suggesting IGFBP-5 may have a survival function in response to apoptotic stimuli (20,21). A similar conclusion was reached by Roschier et al. (22) following their demonstration that induction of apoptosis...

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Prognostic Significance of Insulin-like Growth Factor-Binding Protein Expression in Axillary Lymph Node-Negative Breast Cancer

Abstract: These data suggest that the IGFBPs may play a role in breast cancer biology and that BP-4 levels, analyzed in conjunction with tumor size, may have prognostic significance.

Cited by 38 publications

References 0 publications

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines

IGFBP2 and IGFBP3 Protein Expressions in Human Breast Cancer: Association with Hormonal Factors and Obesity

Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo

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