Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity
Seon-Ah Ha
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSeung Min Shin
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHyun Kee Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSanghee Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHong Namkoong
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYoun Soo Lee
Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHae Joo Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang Min Jung
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYu Sun Lee
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYeun Jun Chung
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYong Gyu Park
Department of Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang Seol Jung
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jin Woo Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to: Jin Woo KIM, Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea.Tel.: 82-2-590-2389Fax: 82-2-593-2389E-mail: [email protected]Search for more papers by this authorSeon-Ah Ha
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSeung Min Shin
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHyun Kee Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSanghee Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHong Namkoong
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYoun Soo Lee
Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHae Joo Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang Min Jung
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYu Sun Lee
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYeun Jun Chung
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorYong Gyu Park
Department of Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang Seol Jung
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jin Woo Kim
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to: Jin Woo KIM, Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea.Tel.: 82-2-590-2389Fax: 82-2-593-2389E-mail: [email protected]Search for more papers by this authorAbstract
Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer. In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk.
References
- 1 Ko J, Lee YH, Hwang SY, et al . Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization. Oncogene. 2003; 22: 4679–89.
- 2 Jung SS, Park HS, Lee IJ, et al . The HCCR oncoprotein as a biomarker for human breast cancer. Clin Can Res. 2005; 11: 7700–8.
- 3 Lamerz R, Stieber P, Fateh-Moghadam A. Serum marker combinations in human breast cancer (review). In Vivo. 1993; 7: 607–14.
- 4 Cho GW, Shin SM, Namkoong H, et al . The phosphatidylinositol 3-kinase/Akt pathway regulates the HCCR-1 oncogene expression. Gene. 2006; 384: 18–26.
- 5 Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988; 240: 622–30.
- 6 Browning PJ, Roberts DD, Zabrenetzky V, et al . Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi’s sarcoma-like lesions in BALB/c nu/nu mice. J Exp Med. 1994; 180: 1949–54.
- 7 Vogel T, Guo NH, Guy R, et al . Apolipoprotein E: a potent inhibitor of endothelial and tumor cell proliferation. J Cell Biochem. 1994; 54: 299–308.
- 8 Huang Z, Hankinson SE, Colditz GA, et al . Dual effects of weight and weight gain on breast cancer risk. JAMA. 1997; 278: 1407–11.
- 9 van den Brandt PA, Spiegelman D, Yaun SS, et al . Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000; 152: 514–27.
- 10 Lahmann PH, Hoffmann K, Allen N, et al . Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). Int J Cancer. 2004; 111: 762–71.
- 11 Lorincz AM, Sukumar S. Molecular links between obesity and breast cancer. Endocr Relat Cancer. 2006; 13: 279–92.
- 12 van Landeghem AA, Poortman J, Nabuurs M, et al . Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res. 1985; 45: 2900–6.
- 13 Goodwin PJ, Ennis M, Pritchard KI, et al . Fasting insulin and outcome in early stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002; 20: 42–51.
- 14 Dizdar O, Alyamac E. Obesity: an endocrine tumor? Med Hypotheses. 2004; 63: 790–2.
- 15 Gordon JW, Ruddle FH. Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Methods Enzymol. 1983; 101: 411–33.
- 16 Vatten LJ, Foss OP. Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women. Cancer Res. 1990; 50: 2341–6.
- 17 Kumar K, Sachdanandam P, Arivazhagan R. Studies on the changes in plasma lipids and lipoproteins in patients with benign and malignant breast cancer. Biochemistry. 1991; 23: 581–9.
- 18 Agurs-Collins T, Kim KS, Dunston GM, et al . Plasma lipid alterations in African-American women with breast cancer. J Cancer Res Clin Oncol. 1998; 124: 186–90.
- 19 Chlebowski RT, Chen Z, Anderson G. Ethnicity and breast cancer in the Women’s Health Initiative: a unifying concept for unfavorable outcome in African American women. Proc Am Soc Clin Oncol. 2004; 23: 99s.
- 20 Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol. 2002; 20: 1128–43.
- 21 Key TJ, Appleby PN, Reeves GK, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 2003; 95: 1218–26.
- 22 Enger SM, Greif JM, Polikoff J, et al. Body weight correlates with mortality in early stage breast cancer. Arch Surg. 2004; 139: 954–60.
- 23 Chlebowski RT. Obesity and early-stage breast cancer. J Clin Oncol. 2005; 23: 1345–7.
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