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Published in: Breast Cancer Research and Treatment 3/2008

01-12-2008 | Preclinical Study

Characterisation of aromatase expression in the human adipocyte cell line SGBS

Authors: Kerry J. McInnes, Kristy A. Brown, Kevin C. Knower, Ashwini L. Chand, Colin D. Clyne, Evan R. Simpson

Published in: Breast Cancer Research and Treatment | Issue 3/2008

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Abstract

Aromatase is a member of the cytochrome P450 superfamily of enzymes which catalyses the rate-limiting step in the biosynthesis of estrogens. A number of clinical studies have highlighted the importance of local estrogen production in adipose tissue. In particular, in the postmenopausal woman, the degree of her estrogenization is mainly determined by the extent of her adiposity and it is this extragonadal source of estrogen that likely contributes to breast cancer development and progression. The mechanisms regulating aromatase expression in adipose tissue however, have not been fully elucidated. In this study, we have characterised the expression of aromatase and its activity in a human preadipocyte cell strain, SGBS. Aromatase is expressed in SGBS cells and its expression and activity are strongly stimulated by forskolin (FSK) and phorbol 12-myristate-13-acetate (PMA) treatment. Consistent with this, FSK and PMA treatment also increased activation of the proximal aromatase promoter, promoter II. These findings mimic those that have previously been shown in isolated primary human preadipocytes. These data suggest that SGBS cells are a valuable model with which to further elucidate the mechanisms regulating aromatase expression, and therefore local estrogen synthesis in human adipose tissue.
Literature
1.
go back to reference Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD, Mendelson CR, Bulun SE (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355PubMedCrossRef Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD, Mendelson CR, Bulun SE (1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342–355PubMedCrossRef
2.
go back to reference McNatty KP, Baird DT, Bolton A, Chambers P, Corker CS, Maclean H (1976) Concentration of oestrogens and androgens in human ovarian venous plasma and follicular fluid throughout the menstrual cycle. J Endocrinol 71:77–85PubMedCrossRef McNatty KP, Baird DT, Bolton A, Chambers P, Corker CS, Maclean H (1976) Concentration of oestrogens and androgens in human ovarian venous plasma and follicular fluid throughout the menstrual cycle. J Endocrinol 71:77–85PubMedCrossRef
3.
go back to reference Doody K, Lorence MC, Mason JI, Simpson ER (1990) Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. J Clin Endocrinol Metab 70:1041–1045PubMed Doody K, Lorence MC, Mason JI, Simpson ER (1990) Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. J Clin Endocrinol Metab 70:1041–1045PubMed
4.
go back to reference Tsai-Morris CH, Aquilano DR, Dufau ML (1985) Cellular localization of rat testicular aromatase activity during development. Endocrinology 116:31–17PubMed Tsai-Morris CH, Aquilano DR, Dufau ML (1985) Cellular localization of rat testicular aromatase activity during development. Endocrinology 116:31–17PubMed
5.
go back to reference Bulun SE, Simpson ER (1994) Regulation of aromatase expression in human tissues. Breast Cancer Res Treat 30:19–29PubMedCrossRef Bulun SE, Simpson ER (1994) Regulation of aromatase expression in human tissues. Breast Cancer Res Treat 30:19–29PubMedCrossRef
6.
go back to reference 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 57:359–383PubMedCrossRef 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 57:359–383PubMedCrossRef
7.
go back to reference 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 270:16449–16457PubMedCrossRef 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 270:16449–16457PubMedCrossRef
8.
go back to reference Clyne CD, Speed CJ, Zhou J, Simpson ER (2002) Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 277:20591–20597PubMedCrossRef Clyne CD, Speed CJ, Zhou J, Simpson ER (2002) Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 277:20591–20597PubMedCrossRef
9.
go back to reference Simpson ER, Zhao Y, Agarwal VR, Michael MD, Bulun SE, Hinshelwood MM, Graham-Lorence S, Sun S, Fisher T, Mendelson CR (1997) Aromatase expression in health and disease. Recent Prog Horm Res 52:185–213PubMed Simpson ER, Zhao Y, Agarwal VR, Michael MD, Bulun SE, Hinshelwood MM, Graham-Lorence S, Sun S, Fisher T, Mendelson CR (1997) Aromatase expression in health and disease. Recent Prog Horm Res 52:185–213PubMed
10.
go back to reference Thorsen T, Tangen M, Stoa KF (1982) Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol. Eur J Cancer Clin Oncol 18:333–337PubMedCrossRef Thorsen T, Tangen M, Stoa KF (1982) Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol. Eur J Cancer Clin Oncol 18:333–337PubMedCrossRef
11.
go back to reference van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH (1985) Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 45:2900–2906PubMed van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH (1985) Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 45:2900–2906PubMed
12.
go back to reference 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 77:1622–1628PubMedCrossRef 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 77:1622–1628PubMedCrossRef
13.
go back to reference Harada N (1997) Aberrant expression of aromatase in breast cancer tissues. J Steroid Biochem Mol Biol 61:175–184PubMedCrossRef Harada N (1997) Aberrant expression of aromatase in breast cancer tissues. J Steroid Biochem Mol Biol 61:175–184PubMedCrossRef
14.
go back to reference Means GD, Mahendroo M, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER (1989) Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem 264:19385–19391PubMed Means GD, Mahendroo M, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER (1989) Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem 264:19385–19391PubMed
15.
go back to reference Harada N, Yamada K, Saito K, Kibe N, Dohmae S, Takagi Y (1990) Structural characterization of the human estrogen synthetase (aromatase) gene. Biochem Biophys Res Commun 166:365–372PubMedCrossRef Harada N, Yamada K, Saito K, Kibe N, Dohmae S, Takagi Y (1990) Structural characterization of the human estrogen synthetase (aromatase) gene. Biochem Biophys Res Commun 166:365–372PubMedCrossRef
16.
go back to reference Toda K, Terashima M, Kawamoto T, Sumimoto H, Yokohama Y, Kuribayashi I, Mitsuuchi Y, Maeda T, Yamamoto Y, Sagara Y, Ikeda H, Shizuta Y (1990) Structural and functional characterization of human aromatase P-450 gene. Eur J Biochem 193:559–565PubMedCrossRef Toda K, Terashima M, Kawamoto T, Sumimoto H, Yokohama Y, Kuribayashi I, Mitsuuchi Y, Maeda T, Yamamoto Y, Sagara Y, Ikeda H, Shizuta Y (1990) Structural and functional characterization of human aromatase P-450 gene. Eur J Biochem 193:559–565PubMedCrossRef
17.
go back to reference Means GD, Kilgore MW, Mahendroo MS, Mendelson CR, Simpson ER (1991) Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. Mol Endocrinol 5:2005–2013PubMed Means GD, Kilgore MW, Mahendroo MS, Mendelson CR, Simpson ER (1991) Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. Mol Endocrinol 5:2005–2013PubMed
18.
go back to reference Mahendroo MS, Means GD, Mendelson CR, Simpson ER (1991) Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem 266:11276–11281PubMed Mahendroo MS, Means GD, Mendelson CR, Simpson ER (1991) Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem 266:11276–11281PubMed
19.
go back to reference Toda K, Shizuta Y (1993) Molecular cloning of a cDNA showing alternative splicing of the 5′-untranslated sequence of mRNA for human aromatase P-450. Eur J Biochem 213:383–389PubMedCrossRef Toda K, Shizuta Y (1993) Molecular cloning of a cDNA showing alternative splicing of the 5′-untranslated sequence of mRNA for human aromatase P-450. Eur J Biochem 213:383–389PubMedCrossRef
20.
go back to reference Mahendroo MS, Mendelson CR, Simpson ER (1993) Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 268:19463–19470PubMed Mahendroo MS, Mendelson CR, Simpson ER (1993) Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 268:19463–19470PubMed
21.
go back to reference 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 90:11312–11316PubMedCrossRef 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 90:11312–11316PubMedCrossRef
22.
go back to reference Zhao Y, Agarwal VR, Mendelson CR, Simpson ER (1997) Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. J Steroid Biochem Mol Biol 61:203–210PubMedCrossRef Zhao Y, Agarwal VR, Mendelson CR, Simpson ER (1997) Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. J Steroid Biochem Mol Biol 61:203–210PubMedCrossRef
23.
go back to reference Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER (1996) Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 81:3843–3849PubMedCrossRef Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER (1996) Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 81:3843–3849PubMedCrossRef
24.
go back to reference Zhou D, Zhou C, Chen S (1997) Gene regulation studies of aromatase expression in breast cancer and adipose stromal cells. J Steroid Biochem Mol Biol 61:273–280PubMedCrossRef Zhou D, Zhou C, Chen S (1997) Gene regulation studies of aromatase expression in breast cancer and adipose stromal cells. J Steroid Biochem Mol Biol 61:273–280PubMedCrossRef
25.
go back to reference Wabitsch M, Brenner RE, Melzner I, Möller P, Heinze E, Debatin K-M, Hauner H (2001) Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Inter J of Obesity 25:8–15CrossRef Wabitsch M, Brenner RE, Melzner I, Möller P, Heinze E, Debatin K-M, Hauner H (2001) Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Inter J of Obesity 25:8–15CrossRef
26.
go back to reference Newell FS, Su H, Tornqvist H, Whitehead JP, Prins JB, Hutley LJ (2006) Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation. FASEB J 20:E2133–E2145CrossRef Newell FS, Su H, Tornqvist H, Whitehead JP, Prins JB, Hutley LJ (2006) Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation. FASEB J 20:E2133–E2145CrossRef
27.
go back to reference Ackerman GE, Smith ME, Mendelson CR, Macdonald PC, Simpson ER (1981) Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 53:412–417PubMedCrossRef Ackerman GE, Smith ME, Mendelson CR, Macdonald PC, Simpson ER (1981) Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 53:412–417PubMedCrossRef
28.
go back to reference Sasano H, Anderson TJ, Silverberg SG, Santen RJ, Conway M, Edwards DP, Krause A, Bhatnagar AS, Evans DB, Miller WR (2005) The validation of new aromatase monoclonal antibodies for immunohistochemistry—a correlation with biochemical activities in 46 cases of breast cancer. J Steroid Biochem Mol Biol 95:35–39PubMedCrossRef Sasano H, Anderson TJ, Silverberg SG, Santen RJ, Conway M, Edwards DP, Krause A, Bhatnagar AS, Evans DB, Miller WR (2005) The validation of new aromatase monoclonal antibodies for immunohistochemistry—a correlation with biochemical activities in 46 cases of breast cancer. J Steroid Biochem Mol Biol 95:35–39PubMedCrossRef
29.
go back to reference Bulun SE, Simpson ER (1994) Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 78:428–432PubMedCrossRef Bulun SE, Simpson ER (1994) Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 78:428–432PubMedCrossRef
30.
go back to reference Price T, O’Brien S, Dunaif A, Simpson ER (1994) Comparison of aromatase cytochrome P450 mRNA levels in adipose tissue from the abdomen and buttock using competitive polymerase chain reaction amplification. Proc Soc Gynecol Invest 39:179 Price T, O’Brien S, Dunaif A, Simpson ER (1994) Comparison of aromatase cytochrome P450 mRNA levels in adipose tissue from the abdomen and buttock using competitive polymerase chain reaction amplification. Proc Soc Gynecol Invest 39:179
31.
go back to reference Forest C, Czerucka D, Negrel R, Ailhaud G (1983) Establishment of a human cell line after transformation by a plasmid containing the early region of the SV40 genome. Cell Biol Int Rep 7:73–81PubMedCrossRef Forest C, Czerucka D, Negrel R, Ailhaud G (1983) Establishment of a human cell line after transformation by a plasmid containing the early region of the SV40 genome. Cell Biol Int Rep 7:73–81PubMedCrossRef
32.
go back to reference Simpson ER (2000) Biology of aromatase in the mammary gland. J Mamm Gland Biol Neo 5:251–258CrossRef Simpson ER (2000) Biology of aromatase in the mammary gland. J Mamm Gland Biol Neo 5:251–258CrossRef
33.
go back to reference Ailhaud G, Hauner H (1997) Development of white adipose tissue. In: Bray G, Bouchard C, James WPT (eds) Handbook of obesity, 2nd edn. Marcel Dekker, New York, p 359 Ailhaud G, Hauner H (1997) Development of white adipose tissue. In: Bray G, Bouchard C, James WPT (eds) Handbook of obesity, 2nd edn. Marcel Dekker, New York, p 359
34.
go back to reference Yamada K, Harada N (1990) Expression of estrogen synthetase (P-450 aromatase) during adipose differentiation of 3T3-L1 cells. Biochem Biophys Res Comm 169:531–536PubMedCrossRef Yamada K, Harada N (1990) Expression of estrogen synthetase (P-450 aromatase) during adipose differentiation of 3T3-L1 cells. Biochem Biophys Res Comm 169:531–536PubMedCrossRef
35.
go back to reference Chen D, Reierstad S, Lin Z, Lu M, Brooks C, Li N, Innes J, Bulun SE (2007) Prostaglandin E(2) induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH(2)-terminal kinase in adipose fibroblasts. Cancer Res 67:8914–8922PubMedCrossRef Chen D, Reierstad S, Lin Z, Lu M, Brooks C, Li N, Innes J, Bulun SE (2007) Prostaglandin E(2) induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH(2)-terminal kinase in adipose fibroblasts. Cancer Res 67:8914–8922PubMedCrossRef
36.
go back to reference Morales L, Neven P, Paridaens R (2005) Choosing between an aromatase inhibitor and tamoxifen in the adjuvant setting. Curr Opin Oncol 17:559–565PubMedCrossRef Morales L, Neven P, Paridaens R (2005) Choosing between an aromatase inhibitor and tamoxifen in the adjuvant setting. Curr Opin Oncol 17:559–565PubMedCrossRef
Metadata
Title
Characterisation of aromatase expression in the human adipocyte cell line SGBS
Authors
Kerry J. McInnes
Kristy A. Brown
Kevin C. Knower
Ashwini L. Chand
Colin D. Clyne
Evan R. Simpson
Publication date
01-12-2008
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9883-2

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