Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells
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Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.
Abstract
Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.
참고문헌 (35)
- Zhang Y, "Positional cloning of the mouse obese gene and its human homologue", Nature, 372, pp.425~432 (1994)
- Huang L, "Leptin : a multifunctional hormone", Cell Res, 10, pp.81~92 (2000)
- Friedman JM, "Leptin and the regulation of body weight in mammals", Nature, 395, pp.763~770 (1998)
- Margetic S, "Leptin : a review of its peripheral actions and interactions", Int J Obes Relat Metab Disord, 26, pp.1407~1433 (2002)
- Hu X, "Leptin--a growth factor in normal and malignant breast cells and for normal mammary gland development", J Natl Cancer Inst, 94, pp.1704~1711 (2002)
- Laud K, "Identification of leptin receptors in human breast cancer : functional activity in the T47-D breast cancer cell line", Mol Cell Endocrinol, 188, pp.219~226 (2002)
- Okumura M, "Leptin and high glucose stimulate cell proliferation in MCF-7human breast cancer cells : reciprocal involvement of PKC-alpha and PPAR expression", Biochim Biophys Acta, 1592, pp.107~116 (2002)
- Somasundar P, "Differential effects of leptin on cancer in vitro", J Surg Res, 113, pp.50~55 (2003)
- Ishikawa M, "Enhanced expression of leptin and leptin receptor(OB-R)in human breast cancer", Clin Cancer Res, 10, pp.4325~4331 (2004)
- O'Brien S N, "Presence of leptin in breast cell lines and breast tumors", Biochem Biophys Res Commun, 259, pp.695~698 (1999)
- Garofalo C, "Increased expression of leptin and the leptin receptor as a marker of breast cancer progression : possible role of obesity-related stimuli", Clin Cancer Res, 12, pp.1447~1453 (2006)
- Guo S, "Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells", Biochim Biophys Acta, 1825, pp.207~222 (2012)
- Tartaglia LA, "Identification and expression cloning of a leptin receptor, OB-R", Cell, 83, pp.1263~1271 (1995)
- Perera CN, "Leptin-regulated gene expression in MCF-7 breast cancer cells : mechanistic insights into leptin-regulated mammary tumor growth and progression", J Endocrinol, 199, pp.221~233 (2008)
- LeRoith D, "The insulin-like growth factor system and cancer", Cancer Lett, 195, pp.127~137 (2003)
- Rajski M, "IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients", BMC Med, 8, pp.1~ (2010)
- Christopoulos PF, "The role of the insulin-like growth factor-1 system in breast cancer", Mol Cancer, 14, pp.43~ (2015)
- Ma J, "Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor(IGF)-I and IGF-binding protein-3", J Natl Cancer Inst, 91, pp.620~625 (1999)
- Chan JM, "Plasma insulin-like growth factor-I and prostate cancer risk : a prospective study", Science, 279, pp.563~566 (1998)
- Endogenous H, "Insulin-like growth factor 1(IGF1), IGF binding protein 3(IGFBP3), and breast cancer risk : pooled individual data analysis of 17 prospective studies", Lancet Oncol, 11, pp.530~542 (2010)
- Ajuwon KM, "The regulation of IGF-1 by leptin in the pig is tissue specific and independent of changes in growth hormone", J Nutr Biochem, 14, pp.522~530 (2003)
- Douros JD, "Control of leptin by metabolic state and its regulatory interactions with pituitary growth hormone and hepatic growth hormone receptors and insulin like growth factors in the tilapia(Oreochromis mossambicus)", Gen Comp Endocrinol, 240, pp.227~237 (2017)
- Daughaday WH, "Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations", Endocr Rev, 10, pp.68~91 (1989)
- Tollet P, "Growth hormone(GH)regulation of cytochrome P-450IIC12, insulin-like growth factor-I(IGF-I), and GH receptor messenger RNA expression in primary rat hepatocytes : a hormonal interplay with insulin, IGF-I, and thyroid hormone", Mol Endocrinol, 4, pp.1934~1942 (1990)
- Rogers SA, "Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor", J Clin Invest, 87, pp.347~351 (1991)
- McCarthy TL, "Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone", Endocrinology, 124, pp.1247~1253 (1989)
- Jansen E, "Identification of multiple transcription start sites in the human insulin-like growth factor-I gene", Mol Cell Endocrinol, 78, pp.115~125 (1991)
- Angel P, "The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation", Biochim Biophys Acta, 1072, pp.129~157 (1991)
- Shen Q, "The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors", Oncogene, 27, pp.366~377 (2008)
- Catalano S, "Leptin enhances, via AP-1, expression of aromatase in the MCF-7cell line", J Biol Chem, 278, pp.28668~28676 (2003)
- Saxena NK, "Bidirectional crosstalk between leptin and insulin-like growth factor-I signaling promotes invasion and migration of breast cancer cells via transactivation of epidermal growth factor receptor", Cancer Res, 68, pp.9712~9722 (2008)
- Ahima RS, "Leptin signaling", Physiol Behav, 81, pp.223~241 (2004)
- Grothey A, "The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors", J Cancer Res Clin Oncol, 125, pp.166~173 (1999)
- Son SW, "Regulatory mechanism of TNFalpha autoregulation in HaCaT cells : the role of the transcription factor EGR-1", Biochem Biophys Res Commun, 374, pp.777~782 (2008)
- Shin SY, "Novel antimitotic activity of 2-hydroxy-4-methoxy-2', 3'-benzochalcone(HymnPro)through the inhibition of tubulin polymerization", J Agric Food Chem, 61, pp.12588~12597 (2013)
