title: Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity.
abstract: 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.
authors.affiliation: Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seon-Ah
authors.initials: SA
authors.lastname: Ha
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Shin
authors.forename: Hyun Kee
authors.initials: HK
authors.lastname: Kim
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.forename: Hong
authors.initials: H
authors.lastname: Namkoong
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Hae Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Jung
authors.forename: Yu Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Yeun Jun
authors.initials: YJ
authors.lastname: Chung
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Sang Seol
authors.initials: SS
authors.lastname: Jung
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009765:Obesity / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C516325:HCCR1 protein, mouse; C476732:LETMD1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface