A gene transcription signature of obesity in breast cancer
Abstract Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of 103 tumors for which the patients’ body mass index (BMI) was ascertained. Sample profiles were stratified according to patients’ obesity phenotype defined as normal (BMI < 25), overweight (BMI 25–29.9), or obese (BMI ≥ 30). Widespread gene expression alterations were evident in breast tumors from obese patients as compared to other tumors, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. In multiple public expression data sets of breast cancers (representing > 1,500 patients), manifestation of the obesity signature patterns correlated with manifestation of a gene signature for IGF signaling and (to a lesser extent) with lower levels of estrogen receptor. In one patient cohort, manifestation of the obesity signature correlated with shorter time to metastases. A number of small molecules either induced or suppressed the obesity-associated transcriptional program in vitro; estrogens alpha-estradiol, levonorgestrel, and hexestrol induced the program, while several anti-parkinsonian agents targeting neurotransmitter receptor pathways repressed the program. Obesity in breast cancer patients appears to impact the gene expression patterns of the tumor (perhaps as a result of altered body chemistry). These results warrant further investigation of obesity-associated modifiers of breast cancer risk and disease outcome..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:132 |
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| Enthalten in: |
Breast cancer research and treatment - 132(2011), 3 vom: 13. Juli, Seite 993-1000 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Creighton, Chad J. [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
BMI |
| Anmerkungen: |
© Springer Science+Business Media, LLC. 2011 |
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| doi: |
10.1007/s10549-011-1595-y |
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| funding: |
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| PPN (Katalog-ID): |
OLC2045976629 |
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| 520 | |a Abstract Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of 103 tumors for which the patients’ body mass index (BMI) was ascertained. Sample profiles were stratified according to patients’ obesity phenotype defined as normal (BMI < 25), overweight (BMI 25–29.9), or obese (BMI ≥ 30). Widespread gene expression alterations were evident in breast tumors from obese patients as compared to other tumors, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. In multiple public expression data sets of breast cancers (representing > 1,500 patients), manifestation of the obesity signature patterns correlated with manifestation of a gene signature for IGF signaling and (to a lesser extent) with lower levels of estrogen receptor. In one patient cohort, manifestation of the obesity signature correlated with shorter time to metastases. A number of small molecules either induced or suppressed the obesity-associated transcriptional program in vitro; estrogens alpha-estradiol, levonorgestrel, and hexestrol induced the program, while several anti-parkinsonian agents targeting neurotransmitter receptor pathways repressed the program. Obesity in breast cancer patients appears to impact the gene expression patterns of the tumor (perhaps as a result of altered body chemistry). These results warrant further investigation of obesity-associated modifiers of breast cancer risk and disease outcome. | ||
| 650 | 4 | |a Obesity | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a BMI | |
| 650 | 4 | |a Insulin-like growth factor | |
| 650 | 4 | |a IGF | |
| 650 | 4 | |a Gene expression profiling | |
| 700 | 1 | |a Sada, Yvonne H. |4 aut | |
| 700 | 1 | |a Zhang, Yiqun |4 aut | |
| 700 | 1 | |a Tsimelzon, Anna |4 aut | |
| 700 | 1 | |a Wong, Helen |4 aut | |
| 700 | 1 | |a Dave, Bhuvanesh |4 aut | |
| 700 | 1 | |a Landis, Melissa D. |4 aut | |
| 700 | 1 | |a Bear, Harry D. |4 aut | |
| 700 | 1 | |a Rodriguez, Angel |4 aut | |
| 700 | 1 | |a Chang, Jenny C. |4 aut | |
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