Abstract
Aims
Previous studies have shown that oestrogen and Insulin-like Growth Factor-1 (IGF-1) act synergistically and cross-stimulatory while the oestrogen receptor (ER) and␣IGF-1R downstream signalling pathways interact at many levels. We investigate the relationship between the ER, and IGF-1R and their ligands in a series of human breast cancer tissue and adjacent non-cancerous tissue (ANCT).
Methods
A series of 139 pairs of breast cancer tissue and ANCT were obtained and divided into ER positive and ER negative groups based on tumour ER alpha immunostaining. All samples were processed for real-time quantitative-PCR to measure IGF-1, IGF-1R, ER alpha, STS and Cyp-19 mRNA levels. In addition, ER positive MCF-7 and ER negative MDA-MB-231 cell lines were treated separately with IGF-1 and an IGF-1R inhibitor called Tyrphostin AG1024 to see the effects of stimulating and inhibiting the IGF-1R. MCF-7 cell line was also treated with 4-hydroxytamoxifen. The mRNA levels of IGF-1, IGF-1R, ER alpha, STS and Cyp-19 of treated cell lines were measured and compared to those of non-treated controls. Data generated was normalised to Cytokeratin-19 mRNA levels.
Results
IGF-1R expression was higher in tumour tissue compared to ANCT (P=0.038) while IGF-1 expression was marginally higher in ANCT compared to tumour tissue only in the ER positive samples (P=0.098). ER positive tumours had a higher expression of IGF-1 compared to ER negative tumours (P=0.001) while IGF-1R, STS and Cyp-19 expression were higher in ER negative tumours (P=0.000, 0.000 and 0.006 respectively). There was no difference in STS or Cyp-19 expression in tumours or ANCT. Using Spearman’s Correlation test, IGF-1 positively correlated with STS, Cyp-19 and ER alpha in ER positive and negative groups (Coefficient=+0.497, +0.662 and +0.651 respectively, P=0.000 in all). IGF-1R correlated with IGF-1, STS, Cyp-19 and ER alpha only in the ER negative tumours (Coefficient=+0.620, +0.394, +0.692 and +0.662 respectively, P=0.000, 0.012, 0.000 and 0.000 respectively). In cell lines, IGF-1 treatment led to an increase in the mean expression of IGF-1, IGF-1R, STS and Cyp-19 in both cell lines while ER alpha expression increased only in MCF-7. IGF-1R inhibition caused a decrease in expression of all five genes in MDA-MB-231 but not in the MCF-7 cell line. Treatment with 4-hydroxytamoxifen caused a decrease in expression of all five genes.
Conclusions
IGF-1R is over-expressed in malignant tissue. IGF-1 is expressed at higher levels in ER positive tumours probably as a result of oestrogen stimulation while IGF-1R expression is higher in ER negative samples as an adaptation to lower local IGF-1 levels. An IGF-1 paracrine relationship may exist between tumour and ANCT but for STS and Cyp-19, there may be an autocrine–paracrine relationship. The IGF-1 ligand-receptor system is an important regulator of oestrogen production while oestrogen may be involved in stimulating IGF-1 expression. The expression of oestrogen synthesising enzymes is higher in ER negative breast cancers which may be due to the lack of oestrogen negative feedback or contribution from the overexpression of IGF-1R.
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References
Adams TE, Epa VC, Garrett TP, Ward CW (2000) Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 57:1050–1093
Agarwal VR, Ashanullah CI, Simpson ER, Bulun SE (1997) Alternatively spliced transcripts of the aromatase cytochrome P450 (CYP19) gene in adipose tissue of women. J Clin Endocrinol Metab 82:70–74
Bartucci M, Morelli C, Mauro L, Ando’ S, Surmacz E (2001) Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Cancer Res 61:6747–6754
Baserga R (1999) The IGF-I receptor in cancer research. Exp Cell Res 253:1–6
Baserga R, Hongo A, Rubini M, Prisco M, Valentinis B (1997) The IGF-I receptor in cell growth, transformation and apoptosis. Biochim Biophys Acta 1332:F105–F126
Beatson GT (2006) On the treatment of inoperable cases of carcinoma of the mamma: suggestion for a new method of treatment, with illustrative cases. Lancet [1896] 104–107
Bonneterre J, Peyrat JP, Beuscart R, Demaille A (1990) Prognostic significance of insulin-like growth factor 1 receptors in human breast cancer. Cancer Res 50:6931–6935
Brodie A, Lu Q, Nakamura J (1997) Aromatase in the normal breast and breast cancer. J Steroid Biochem Mol Biol 61:281–286
Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, Martin R, Utsunomiya H, Thung S, Gurates B, Tamura M, Langoi D, Deb S (2005) Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev 57:359–383
Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER (1993) A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab 77:1622–1628
Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72:23–27
Chong YM, Williams SL, Elkak A, Sharma AK, Mokbel K (2006) Insulin-like growth factor 1 (IGF-1) and its receptor mRNA levels in breast cancer and adjacent non-neoplastic tissue. Anticancer Res 26:167–173
Colletti RB, Roberts JD, Devlin JT, Copeland KC (1989) Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer. Cancer Res 49:1882–1884
Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092
Coppola D, Ferber A, Miura M, Sell C, D’Ambrosio C, Rubin R, Baserga R (1994) A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. Mol Cell Biol 14:4588–4595
Crichton MB, Nichols JE, Zhao Y, Bulun SE, Simpson ER (1996) Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells. Mol Cell Endocrinol 118:215–220
Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23:7721–7735
Cullen KJ, Allison A, Martire I, Ellis M, Singer C (1992) Insulin-like growth factor expression in breast cancer epithelium and stroma. Breast Cancer Res Treat 22:21–29
Cullen KJ, Yee D, Sly WS, Perdue J, Hampton B, Lippman ME, Rosen N (1990) Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res 50:48–53
DeAngelis T, Ferber A, Baserga R (1995) Insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the platelet-derived growth factor receptor. J Cell Physiol 164:214–221
Dowsett M, Smithers D, Moore J, Trunet PF, Coombes RC, Powles TJ, Rubens R, Smith IE (1994) Endocrine changes with the aromatase inhibitor fadrozole hydrochloride in breast cancer. Eur J Cancer 30A:1453–1458
Dupont J, Karas M, LeRoith D (2000) The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components. J Biol Chem 275:35893–35901
Dupont J, Le RD (2001) Insulin-like growth factor 1 and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects. Mol Pathol 54:149–154
Ellis MJ, Jenkins S, Hanfelt J, Redington ME, Taylor M, Leek R, Siddle K, Harris A (1998) Insulin-like growth factors in human breast cancer. Breast Cancer Res Treat 52:175–184
Ellis MJ, Singer C, Hornby A, Rasmussen A, Cullen KJ (1994) Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer. Breast Cancer Res Treat 31:249–261
Esteban JM, Warsi Z, Haniu M, Hall P, Shively JE, Chen S (1992) Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation. Am J Pathol 140:337–343
Gebauer G, Jager W, Lang N (1998) mRNA expression of components of the insulin-like growth factor system in breast cancer cell lines, tissues, and metastatic breast cancer cells. Anticancer Res 18:1191–1195
Gee JM, Robertson JF, Gutteridge E, Ellis IO, Pinder SE, Rubini M, Nicholson RI (2005) Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer. Endocr Relat Cancer 12(Suppl 1):S99–S111
Geier A, Beery R, Haimsohn M, Karasik A (1995) Insulin-like growth factor-1 inhibits cell death induced by anticancer drugs in the MCF-7 cells: involvement of growth factors in drug resistance. Cancer Invest 13:480–486
Geisler J, Berntsen H, Lonning PE (2000) A novel HPLC-RIA method for the simultaneous detection of estrone, estradiol and estrone sulphate levels in breast cancer tissue. J Steroid Biochem Mol Biol 72:259–264
Giudice LC, Dsupin BA, Gargosky SE, Rosenfeld RG, Irwin JC (1994) The insulin-like growth factor system in human peritoneal fluid: its effects on endometrial stromal cells and its potential relevance to endometriosis. J Clin Endocrinol Metab 79:1284–1293
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802
Grodin JM, Siiteri PK, MacDonald PC (1973) Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab 36:207–214
Guerra FK, Eijan AM, Puricelli L, Alonso DF, Bal de Kier JE, Kornblihgtt AR, Charreau EH, Elizalde PV (1996) Varying patterns of expression of insulin-like growth factors I and II and their receptors in murine mammary adenocarcinomas of different metastasizing ability 1. Int J Cancer 65:812–820
Guo YS, Jin GF, Houston CW, Thompson JC, Townsend CM Jr (1998) Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol 175:141–148
Guvakova MA, Surmacz E (1997) Overexpressed IGF-I receptors reduce estrogen growth requirements, enhance survival, and promote E-cadherin-mediated cell–cell adhesion in human breast cancer cells. Exp Cell Res 231:149–162
Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351:1393–1396
Happerfield LC, Miles DW, Barnes DM, Thomsen LL, Smith P, Hanby A (1997) The localization of the insulin-like growth factor receptor 1 (IGFR-1) in benign and malignant breast tissue. J Pathol 183:412–417
Harada N, Utsumi T, Takagi Y (1993) Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci USA 90:11312–11316
Honma N, Takubo K, Sawabe M, Arai T, Akiyama F, Sakamoto G, Utsumi T, Yoshimura N, Harada N (2006) Estrogen-metabolizing enzymes in breast cancers from women over the age of 80. J Clin Endocrinol Metab 91(2):607–613
Jiang WG, Watkins G, Lane J, Cunnick GH, Douglas-Jones A, Mokbel K, Mansel RE (2003) Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers. Clin Cancer Res 9:6432–6440
Kleinman D, Karas M, Roberts CT Jr, LeRoith D, Phillip M, Segev Y, Levy J, Sharoni Y (1995) Modulation of insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol. Endocrinology 136:2531–2537
Kudoh M, Susaki Y, Ideyama Y, Nanya T, Mori M, Shikama H (1997) Inhibitory effects of a novel aromatase inhibitor, YM511, on growth of endometrial explants and insulin-like growth factor-I gene expression in rats with experimental endometriosis. J Steroid Biochem Mol Biol 63:75–80
Lee AV, Cui X, Oesterreich S (2001) Cross-talk among estrogen receptor, epidermal growth factor, and insulin-like growth factor signaling in breast cancer. Clin Cancer Res 7:4429s–4435s
LeRoith D, Roberts CT Jr (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137
Levin ER (2003) Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 17:309–317
Lichtner RB (2003) Estrogen/EGF receptor interactions in breast cancer: rationale for new therapeutic combination strategies. Biomed Pharmacother 57:447–451
Lonning PE, Hall K, Aakvaag A, Lien EA (1992) Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients1. Cancer Res 52:4719–4723
Loriaux DL, Ruder HJ, Lipsett MB (1971) The measurement of estrone sulfate in plasma. Steroids 18:463–472
Martin MB, Franke TF, Stoica GE, Chambon P, Katzenellenbogen BS, Stoica BA, McLemore MS, Olivo SE, Stoica A (2000) A role for Akt in mediating the estrogenic functions of epidermal growth factor and insulin-like growth factor 1. Endocrinology 141:4503–4511
Meng L, Zhou J, Sasano H, Suzuki T, Zeitoun KM, Bulun SE (2001) Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction. Cancer Res 61:2250–2255
Miller WR, Anderson TJ, Jack WJ (1990) Relationship between tumour aromatase activity, tumour characteristics and response to therapy. J Steroid Biochem Mol Biol 37:1055–1059
Miller WR, O’Neill J (1987) The importance of local synthesis of estrogen within the breast. Steroids 50:537–548
Molloy CA, May FE, Westley BR (2000) Insulin receptor substrate-1 expression is regulated by estrogen in the MCF-7 human breast cancer cell line. J Biol Chem 275:12565–12571
Moschos SJ, Mantzoros CS (2002) The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 63:317–332
Nakamura T, Matsumoto K, Kiritoshi A, Tano Y, Nakamura T (1997) Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. Cancer Res 57:3305–3313
Newman SP, Purohit A, Ghilchik MW, Potter BV, Reed MJ (2000) Regulation of steroid sulphatase expression and activity in breast cancer. J Steroid Biochem Mol Biol 75:259–264
Nicholson RI, Hutcheson IR, Knowlden JM, Jones HE, Harper ME, Jordan N, Hiscox SE, Barrow D, Gee JM (2004) Nonendocrine pathways and endocrine resistance: observations with antiestrogens and signal transduction inhibitors in combination. Clin Cancer Res 10:346S–354S
Nicholson RI, Johnston SR (2005) Endocrine therapy—current benefits and limitations. Breast Cancer Res Treat 93(Suppl 1):S3–S10
Nicholson RI, Staka C, Boyns F, Hutcheson IR, Gee JM (2004) Growth factor-driven mechanisms associated with resistance to estrogen deprivation in breast cancer: new opportunities for therapy. Endocr Relat Cancer 11:623–641
O’Neill JS, Elton RA, Miller WR (1988) Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br Med J (Clin Res Ed) 296:741–743
Pasqualini JR, Chetrite G, Blacker C, Feinstein MC, Delalonde L, Talbi M, Maloche C (1996) Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. J␣Clin Endocrinol Metab 81:1460–1464
Pasqualini JR, Chetrite GS (2005) Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer. J Steroid Biochem Mol Biol 93:221–236
Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15:17–35
Pollak M, Costantino J, Polychronakos C, Blauer SA, Guyda H, Redmond C, Fisher B, Margolese R (1990) Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients. J Natl Cancer Inst 82:1693–1697
Pollak MN (1998) Endocrine effects of IGF-I on normal and transformed breast epithelial cells: potential relevance to strategies for breast cancer treatment and prevention. Breast Cancer Res Treat 47:209–217
Purohit A, Chapman O, Duncan L, Reed MJ (1992) Modulation of oestrone sulphatase activity in breast cancer cell lines by growth factors. J Steroid Biochem Mol Biol 41:563–566
Purohit A, Reed MJ (1992) Oestrogen sulphatase activity in hormone-dependent and hormone-independent breast-cancer cells: modulation by steroidal and non-steroidal therapeutic agents. Int J Cancer 50:901–905
Railo MJ, von Smitten K, Pekonen F (1994) The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. Eur J Cancer 30A:307–311
Resnicoff M, Baserga R (1998) The role of the insulin-like growth factor I receptor in transformation and apoptosis. Ann NY Acad Sci 842:76–81
Richards RG, Walker MP, Sebastian J, DiAugustine RP (1998) Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse. J Biol Chem 273:11962–11969
Ruan W, Catanese V, Wieczorek R, Feldman M, Kleinberg DL (1995) Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. Endocrinology 136:1296–1302
Sasano H, Harada N (1998) Intratumoral aromatase in human breast, endometrial, and ovarian malignancies. Endocr Rev 19:593–607
Sasano H, Murakami H (1998) Immunolocalization of aromatase in human breast disorders using different antibodies. Breast Cancer Res Treat 49(Suppl 1):S79–S84
Sell C, Baserga R, Rubin R (1995) Insulin-like growth factor I (IGF-I) and the IGF-I receptor prevent etoposide-induced apoptosis. Cancer Res 55:303–306
Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T, Rubin R, Efstratiadis A, Baserga R (1994) Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. Mol Cell Biol 14:3604–3612
Seslar S, Nakamura T, Byers S (1995) Tumor-stroma interactions and stromal cell density regulate hepatocyte growth factor protein levels: a role for transforming growth factor-beta activation. Endocrinology 136:1945–1953
Shekhar MP, Werdell J, Tait L (2000) Interaction with endothelial cells is a prerequisite for branching ductal-alveolar morphogenesis and hyperplasia of preneoplastic human breast epithelial cells: regulation by estrogen. Cancer Res 60:439–449
Singh A, Reed MJ (1991) Insulin-like growth factor type I and insulin-like growth factor type II stimulate oestradiol-17 beta hydroxysteroid dehydrogenase (reductive) activity in breast cancer cells. J Endocrinol 129:R5–R8
Stewart AJ, Johnson MD, May FE, Westley BR (1990) Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem 265:21172–21178
Suzuki T, Miki Y, Nakata T, Shiotsu Y, Akinaga S, Inoue K, Ishida T, Kimura M, Moriya T, Sasano H (2003) Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. J Steroid Biochem Mol Biol 86:449–454
Svenstrup B, Herrstedt J, Brunner N, Bennett P, Wachmann H, Dombernowsky P (1994) Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A. Eur J Cancer 30A:1254–1258
Tekmal RR, Kirma N, Gill K, Fowler K (1999) Aromatase overexpression and breast hyperplasia, an in vivo model—continued overexpression of aromatase is sufficient to maintain hyperplasia without circulating estrogens, and aromatase inhibitors abrogate these preneoplastic changes in mammary glands. Endocr Relat Cancer 6:307–314
Teruel T, Valverde AM, Benito M, Lorenzo M (1996) Insulin-like growth factor I and insulin induce adipogenic-related gene expression in fetal brown adipocyte primary cultures. Biochem J 319(Pt 2):627–632
Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, Glazer PM (1997) Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 57:3079–3083
Umayahara Y, Kawamori R, Watada H, Imano E, Iwama N, Morishima T, Yamasaki Y, Kajimoto Y, Kamada T (1994) Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer. J Biol Chem 269:16433–16442
Utsumi T, Harada N, Maruta M, Takagi Y (1996) Presence of alternatively spliced transcripts of aromatase gene in human breast cancer. J Clin Endocrinol Metab 81:2344–2349
Valverde AM, Lorenzo M, Navarro P, Benito M (1997) Phosphatidylinositol 3-kinase is a requirement for insulin-like growth factor I-induced differentiation, but not for mitogenesis, in fetal brown adipocytes. Mol Endocrinol 11:595–607
van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH (1985) Endogenous concentration and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 45:2907–2912
van Roozendaal KE, Klijn JG, van Ooijen B, Claassen C, Eggermont AM, Henzen-Logmans SC, Foekens JA (1996) Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breast tissue sources. Int J Cancer 65:120–125
Voskuil DW, Bosma A, Vrieling A, Rookus MA, van’t Veer LJ (2004) Insulin-like growth factor (IGF)-system mRNA quantities in normal and tumor breast tissue of women with sporadic and familial breast cancer risk. Breast Cancer Res Treat 84:225–233
Yee D, Paik S, Lebovic GS, Marcus RR, Favoni RE, Cullen KJ, Lippman ME, Rosen N (1989) Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol 3:509–517
Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489
Yue W, Zhou D, Chen S, Brodie A (1994) A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene. Cancer Res 54:5092–5095
Zhang ZH, Yamashita H, Toyama T, Omoto Y, Sugiura H, Hara Y, Wu X, Iwase H (2006) Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast. Breast Cancer Res 5[2003]:250–256
Zhao Y, Nichols JE, Bulun SE, Mendelson CR, Simpson ER (1995) Aromatase P450 gene expression in human adipose tissue. Role of a Jak/STAT pathway in regulation of the adipose-specific promoter. J Biol Chem 270:16449–16457
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Chong, Y.M., Colston, K., Jiang, W.G. et al. The relationship between the insulin-like growth factor-1 system and the oestrogen metabolising enzymes in breast cancer tissue and its adjacent non-cancerous tissue. Breast Cancer Res Treat 99, 275–288 (2006). https://doi.org/10.1007/s10549-006-9215-y
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DOI: https://doi.org/10.1007/s10549-006-9215-y