HER2 Induces Expression of Leptin in Human Breast Epithelial Cells

Overview

Journal BMB Rep

Specialties Biochemistry
Molecular Biology

Date 2012 Dec 25

PMID 23261058

Citations 11

Authors

Yujin Cha

Youjin Kang

Aree Moon

Affiliations

Soon will be listed here.

Abstract

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ∼30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy. [BMB Reports 2012; 45(12): 719-723].

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References

Ishikawa M, Kitayama J, Nagawa H . Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res. 2004; 10(13):4325-31. DOI: 10.1158/1078-0432.CCR-03-0749. View

Park Y, Lee H, Lee J . Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells. BMB Rep. 2010; 43(2):91-6. DOI: 10.5483/bmbrep.2010.43.2.091. View

Kim M, Lee E, Kim H, Moon A . p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res. 2003; 63(17):5454-61. View

Gambino Y, Maymo J, Perez-Perez A, Duenas J, Sanchez-Margalet V, Calvo J . 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions. Biol Reprod. 2010; 83(1):42-51. DOI: 10.1095/biolreprod.110.083535. View

Song H, Ki S, Kim S, Moon A . Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res. 2006; 66(21):10487-96. DOI: 10.1158/0008-5472.CAN-06-1461. View

Ray A, Nkhata K, Cleary M . Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int J Oncol. 2007; 30(6):1499-509. View

Moon A, Kim M, Kim T, Kim S, Kim H, Chen Y . H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: a role for MMP-2 in the H-ras-induced invasive phenotype. Int J Cancer. 2000; 85(2):176-81. DOI: 10.1002/(sici)1097-0215(20000115)85:2<176::aid-ijc5>3.0.co;2-e. View

Cascio S, Bartella V, Auriemma A, Johannes G, Russo A, Giordano A . Mechanism of leptin expression in breast cancer cells: role of hypoxia-inducible factor-1alpha. Oncogene. 2007; 27(4):540-7. DOI: 10.1038/sj.onc.1210660. View

Garofalo C, Koda M, Cascio S, Sulkowska M, Kanczuga-Koda L, Golaszewska J . Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli. Clin Cancer Res. 2006; 12(5):1447-53. DOI: 10.1158/1078-0432.CCR-05-1913. View

10.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J . Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372(6505):425-32. DOI: 10.1038/372425a0. View

11.

Lee M, Madani S, Sekula D, Sweeney G . Leptin increases expression and activity of matrix metalloproteinase-2 and does not alter collagen production in rat glomerular mesangial cells. Endocr Res. 2005; 31(1):27-37. DOI: 10.1080/07435800500229011. View

12.

Schwartz M, Baskin D, Kaiyala K, Woods S . Model for the regulation of energy balance and adiposity by the central nervous system. Am J Clin Nutr. 1999; 69(4):584-96. DOI: 10.1093/ajcn/69.4.584. View

13.

Porter G, Inglis K, Wood L, Veugelers P . Effect of obesity on presentation of breast cancer. Ann Surg Oncol. 2006; 13(3):327-32. DOI: 10.1245/ASO.2006.03.049. View

14.

Schaffler A, Scholmerich J, Buechler C . Mechanisms of disease: adipokines and breast cancer - endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat Clin Pract Endocrinol Metab. 2007; 3(4):345-54. DOI: 10.1038/ncpendmet0456. View

15.

Saxena N, Taliaferro-Smith L, Knight B, Merlin D, Anania F, ORegan R . 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. 2008; 68(23):9712-22. PMC: 3180854. DOI: 10.1158/0008-5472.CAN-08-1952. View

16.

Gambino Y, Perez Perez A, Duenas J, Calvo J, Sanchez-Margalet V, Varone C . Regulation of leptin expression by 17beta-estradiol in human placental cells involves membrane associated estrogen receptor alpha. Biochim Biophys Acta. 2012; 1823(4):900-10. DOI: 10.1016/j.bbamcr.2012.01.015. View

17.

Vona-Davis L, Howard-McNatt M, Rose D . Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev. 2007; 8(5):395-408. DOI: 10.1111/j.1467-789X.2007.00396.x. View

18.

Kim I, Yong H, Kang K, Moon A . Overexpression of ErbB2 induces invasion of MCF10A human breast epithelial cells via MMP-9. Cancer Lett. 2008; 275(2):227-33. DOI: 10.1016/j.canlet.2008.10.013. View

19.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun M . Cancer statistics, 2007. CA Cancer J Clin. 2007; 57(1):43-66. DOI: 10.3322/canjclin.57.1.43. View

20.

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View