Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

Enriori, Pablo J.; Fischer, Carlos R.; Gori, Jorge R.; Etkin, Alberto E.; Calandra, Ricardo S.; Lüthy, Isabel Alicia

doi:10.1530/eje.0.1480177

Cited by 9 publications

(9 citation statements)

References 27 publications

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“…It is possible that high circulating levels of IGF‐I promote proliferation of the breast tissue through increased IGF‐I binding to its IGF‐I receptors. These results are consistent with previously reported positive associations of elevated IGF‐I levels and of IGF‐I to IGFBP‐3 ratios with benign breast disease,48 and also with the observation of elevated IGF‐I concentrations in Type I breast cysts relative to normal breast tissue 49. Type I cysts originate from the terminal duct lobular units, the site where most proliferative breast lesions occur.…”

Section: Discussionsupporting

confidence: 92%

Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2

Ikle

Elwell

Bryantsev

et al. 2008

Developmental Dynamics

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The myocyte enhancer factor-2 (MEF2) family of transcription factors plays key roles in the activation of muscle structural genes. In Drosophila, MEF2 accumulates at high levels in the embryonic muscles, where it activates target genes throughout the mesoderm. Here, we identify the Transglutaminase gene (Tg; CG7356) as a direct transcriptional target of MEF2 in the cardiac musculature. Tg is expressed in cells forming the inflow tracts of the dorsal vessel, and we identify the enhancer responsible for this expression. The enhancer contains three binding sites for MEF2, and can be activated by MEF2 in tissue culture and in vivo. Moreover, loss of MEF2 function, or removal of the MEF2 binding sites from the enhancer, results in loss of Tg expression. These studies identify a new MEF2 target in the cardiac musculature. These studies provide a possible mechanism for the activation of transglutaminase genes.

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Section: Discussionsupporting

confidence: 92%

Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2

Ikle

Elwell

Bryantsev

et al. 2008

Developmental Dynamics

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“…With respect to SHBG, a very small case–control study (Parlati et al , 1988) has indicated that it may be increased in BBD, whereas another study generated equivocal results (Mancini et al , 1991, with 131 women with breast pathology and use of ‘background normal' levels). Regarding the IGF system, some case–control studies (Enriori et al (2003), with 41 BBD cases and 25 control women; Singer et al (2004), with 23 BBD cases and 38 control women; Barnes et al (2009), with 149 BBD cases and 733 control women) reported that IGF-1 is increased in BBD, a study indicated that in BBD higher levels of IGF-1 reduce the likelihood of lobular involution (Rice et al (2012), a cross-sectional study among 472 women), whereas another case–control study has indicated no association of IGF-1 with proliferative BBD (Su et al (2010), with 359 BBD cases and 359 control women). For IGFBP-3, there have been reports from case–control studies of higher levels in BBD (Holdaway et al (1999), with 12 BBD cases and 43 control women; Su et al (2010), with 359 BBD cases and 359 controls).…”

Section: Discussionmentioning

confidence: 99%

The hormonal profile of benign breast disease

et al. 2012

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Background:Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology.Methods:We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires.Results:Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (−4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (−5.0%, 42.9%) for testosterone; and −5.2% (−13.8%, 4.4%) and −12.1% (−19.8%, −3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD.Conclusions:Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

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“…These results are consistent with previously reported positive associations of elevated IGF-I levels and of IGF-I to IGFBP-3 ratios with benign breast disease, 48 and also with the observation of elevated IGF-I concentrations in Type I breast cysts relative to normal breast tissue. 49 Type I cysts originate from the terminal duct lobular units, the site where most proliferative breast lesions occur. In our study, as is true for any case-control study, proper selection of controls is of paramount importance.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3 and the risk of fibrocystic breast conditions among Chinese women

Chen

Doherty

Lewis

et al. 2005

Intl Journal of Cancer

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We investigated whether circulating insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case-control study nested within a randomized trial of breast self-examination conducted in Shanghai, China. Participants were enrolled during 1989-1991 and were followed over 10 years for the development of breast diseases. Controls (n 5 897) were frequency-matched by age to cases (n 5 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF-I and IGFBP-3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF-I, IGFBP3 and their molar ratio were 3.02 (2.02-4.52), 1.92 (1.37-2.71) and 2.26 (1.52-3.36), respectively. The strength of the association between IGF-I levels and FBC was attenuated after adjustment for IGFBP-3 and that for IGFBP-3 was largely eliminated after adjustment for IGF-I. Increasing levels of IGF-I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF-I: 3.13 (1.50-6.53), 4.57 (2.22-9.39) and 6.30 (3.08-12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF-I may contribute to the development of FBC. ' 2005 Wiley-Liss, Inc.Key words: insulin-like growth factor; insulin-like growth factor binding protein-3; breast cancer; fibrocystic breast conditions; Chinese Insulin-like growth factors (IGFs) are potent mitogenic and anti-apoptotic factors that regulate cell proliferation, differentiation and apoptosis. [1][2][3] The effect of IGFs is modulated by at least 6 high affinity IGF-binding proteins (IGFBPs); 4,5 greater than 95% of circulating IGF-I is complexed with IGFBP-3 and an acid-labile subunit. 6 The majority of IGF-I and IGFBPs are produced by the liver, the rest by a wide variety of tissues. 2 There are several reasons to suspect that the circulating levels of IGF-I and IGFBP-3 could influence breast cancer risk. In in vitro studies, IGF-I modulates gene expression and growth of the breast cancer cell line 8 Expression of IGF-I receptors affect responsiveness of MCF-7 cells to IGF-I and estradiol. 9 Evidence from breast cancer cell lines, experimental animal models and epidemiologic studies suggests that there is a synergistic effect between IGF-I and estrogens and androgens on cell proliferation and breast cancer risk. 10-14 Breast epithelial cells and stromal tissues have been shown to contain IGF-I and IGF-II proteins, [15][16][17][18]19 as well as IGFs mRNA 20,21 and IGF-I receptor. 22 In addition to modulation of IGF availability and action, IGFBPs have been shown to inhibit cellular growth [23][24][25][26] and IGF-I receptor activation, 27 and enhance apoptosis. 28,29 In a mouse mammary model, a reduced circulating IGF-I level delayed the onset of chemically and genet...

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Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

Cited by 9 publications

References 27 publications

Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2

Cardiac expression of the drosophila Transglutaminase (CG7356) gene is directly controlled by myocyte enhancer factor‐2

The hormonal profile of benign breast disease

Insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3 and the risk of fibrocystic breast conditions among Chinese women

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