Insulin-like growth factor expression in breast cancer epithelium and stroma

Cullen, Kevin J.; Allison, Audrey; Martire, Isabella; Ellis, Matthew J.; Singer, Christian F.

doi:10.1007/bf01833330

Cited by 95 publications

(59 citation statements)

References 34 publications

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“…Although IGF-II has a clearly established role in foetal development (Allan et al, 2001), its function in postnatal life is less understood, despite circulating at a much higher concentration than IGF-I. Although experimental evidence suggests that IGF-II can increase the growth of breast cancer cells in vitro (Cullen et al, 1992) and is upregulated in many breast tumours (Li et al, 1998;Fichera et al, 2000), our results show that circulating IGF-II concentration is not strongly associated with subsequent breast cancer risk in pre-or postmenopausal women, which is consistent with evidence from case -control studies (Holdaway et al, 1999;Li et al, 2001;Yu et al, 2002), although Gr nbaek et al (2004) reported in a prospective study an increase in risk of breast cancer among postmenopausal women with increasing IGF-II, which was of borderline statistical significance.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

et al. 2005

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The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case -control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74 -3.95; test for linear trend, P ¼ 0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21 -1.12, P for trend ¼ 0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre-or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer. It is well established that insulin-like growth factor-I (IGF-I) and IGF-II can stimulate cell proliferation and inhibit cell death in many tissue types (Pollak, 2000) including normal and malignant breast cancer cells (Sachdev and Yee, 2001). The bioavailability of circulating IGF ligands is complex; at least six IGF-binding proteins (IGFBPs) have been identified, the most abundant of which is IGFBP-3. This binds approximately 75 -90% of circulating IGF-I and IGF-II and may be the most important determinant of IGF bioavailability (Jones and Clemmons, 1995).There is considerable between-person variation in the circulating concentrations of IGF-I, IGF-II and their binding proteins, believed to be due to genetic and environmental factors (Jones and Clemmons, 1995;Harrela et al, 1996). This variation may be important because epidemiological evidence suggests that elevated levels of serum IGF-I, as absolute concentrations or relative to IGFBP-3, may be associated with an increased risk of breast cancer in premenopausal women (Peyrat et al, 1993;Bruning et al, 1995;Bohlke et al, 1998;Hankinson et al, 1998;Petridou et al, 2000;Toniolo et al, 2000;Kaaks et al, 2002;Krajcik et al, 2002;Muti et al, 2002;Yu et al, 2002;Keinan-Boker et al, 2003). There are limited data on the association between serum IGF-II concentration and breast cancer risk (Holdaway et al, 1999;Li et al, 2001;Yu et al, 2002;Gr nbaek et al, 2004).The aim of this study is to examine the associations between serum concentrations of IGF-I, IGF-II and IGFBP-3 and subsequent breast cancer risk in a case -control study nested within a cohort of women on the island of Guernsey. MATERIALS AND METHODS The Guernsey cohortBetween 1977 and 1991, 6127 women aged 35 years or older who lived on the British island of Guernsey were re...

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Section: Discussionmentioning

confidence: 99%

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

et al. 2005

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“…In analogy to uPA, the relationship of PSA to a poor response to tamoxifen therapy, which does not affect PSA expression in vitro (Zarghami et al, 1997), may, for example, be due to a local increase in the concentration of bioavailable IGFs by cleaving IGFBPs (Cohen et al, 1992(Cohen et al, , 1994Figueroa and Yee, 1992;Kanety et al, 1993) through tumour cell-secreted PSA. The free IGFs, abundantly present around the tumour cells because of the focal action of secreted PSA, are potent mitogens for breast cancer cells (Osborne et al, 1989;Cullen et al, 1990). They may disturb the balance and abolish the growth inhibitory effects induced by tamoxifen, despite a reduction in total serum levels of IGFs (Pollak et al, 1990;Lonning et al, 1992;Yee et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Insulin-like growth factor I and II (IGF-I and -II) are known as potent mitogens for breast cancer cells (Osborne et al, 1989;Cullen et al, 1990). Binding of IGFs to their binding proteins (IGFBPs) can reduce their mitogenic response (Figueroa and Yee, 1992).…”

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confidence: 99%

Expression of prostate-specific antigen (PSA) correlates with poor response to tamoxifen therapy in recurrent breast cancer

Foekens

Diamandis

et al. 1999

Br J Cancer

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Summary Prostate-specific antigen (PSA) is a serine protease which may play a role in a variety of cancer types, including breast cancer. In the present study, we evaluated whether the level of PSA in breast tumour cytosol could be associated with prognosis in primary breast cancer, or with response to tamoxifen therapy in recurrent disease. PSA levels were determined by enzyme-linked immunosorbent assay (ELISA) in breast tumour cytosols, and were correlated with prognosis in 1516 patients with primary breast cancer and with response to first-line tamoxifen therapy in 434 patients with recurrent disease. Relating the levels of PSA with classical prognostic factors, low levels were more often found in larger tumours, tumours of older and post-menopausal patients, and in steroid hormone receptor-negative tumours. There was no significant association between the levels of PSA with grade of differentiation or the number of involved lymph nodes. In patients with primary breast cancer, PSA was not significantly related to the rate of relapse, and a positive association of PSA with an improved survival could be attributed to its relationship to age. In patients with recurrent breast cancer, a high level of PSA was significantly related to a poor response to tamoxifen therapy, and a short progression-free and overall survival after start of treatment for recurrent disease. In Cox multivariate analyses for response to therapy and for (progression-free) survival, corrected for age/menopausal status, disease-free interval, site of relapse and steroid hormone receptor status, PSA was an independent variable of poor prognosis. It is concluded that the level of PSA in cytosols of primary breast tumours might be a marker to select breast cancer patients who may benefit from systemic tamoxifen therapy.

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“…Previous studies of IGF-I expression in mammary tissue from rodents (Kleinberg 1997) and humans (Yee et al 1991, Cullen et al 1992) have shown that IGF-I expression is limited to mammary stromal cells. To test whether this was true in prepubertal heifers, we prepared primary mammary epithelial cells from two prepubertal heifers (Weber et al 1999).…”

Section: Expression Of Mammary Igf-i Mrna Is Exclusive To Mammary Stromamentioning

confidence: 99%

Interactions between the ovary and the local IGF-I axis modulate mammary development in prepubertal heifers

Berry

Howard²,

Jobst³

et al. 2003

Journal of Endocrinology

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The objective was to determine the effects of ovariectomy and epithelial-stromal interactions on mammary development and local expression of IGF-I and IGF-binding protein (IGFBP) mRNA in prepubertal heifers. An epithelium-free ('cleared') fat pad (CFP) was prepared in two glands in each of 14 Holstein heifers, aged 1-3 months. Eight of the calves were also ovariectomized. Serum concentrations of GH, IGF-I and prolactin were not affected by ovariectomy. At 6 months of age, calves were killed to provide mammary samples of parenchyma, CFP and intact fat pad (MFP). Total mammary mass was reduced in ovariectomized calves (130 21 g vs 304 25 g; P<0·001), and in several cases parenchymal tissue was essentially absent. Uterus weight was also reduced by ovariectomy (14·5 3·8 g vs 30·4 4·5 g; P<0·05). In support of our hypothesis that local IGF-I mediates prepubertal mammary development, mRNA expression of IGF-I was lower in ovariectomized than in control calves (62·1 7·8 vs 91·6 7·8 arbitrary units; P<0·05). Specific binding of IGF-I to mammary parenchymal microsomes was also reduced by ovariectomy (377 142 vs 868 82 c.p.m.; P<0·01), suggesting decreased sensitivity to IGF-I. Expression of IGFBP-3 and IGFBP-5 mRNA were not influenced by ovariectomy. Expression of IGF-I, IGFBP-3 and IGFBP-5 mRNA did not differ between CFP and MFP, suggesting that expression of these factors was not influenced by interactions between stroma and developing epithelium. Overall, the data suggested that interactions between the ovary and the local IGF-I axis act to optimize the availability and effectiveness of IGF-I within the gland to stimulate mammary growth.

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Insulin-like growth factor expression in breast cancer epithelium and stroma

Cited by 95 publications

References 34 publications

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

Expression of prostate-specific antigen (PSA) correlates with poor response to tamoxifen therapy in recurrent breast cancer

Interactions between the ovary and the local IGF-I axis modulate mammary development in prepubertal heifers

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