Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity.
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.
Ha
Seon-Ah
SA
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Shin
Seung Min
SM
Kim
Hyun Kee
HK
Kim
Sanghee
S
Namkoong
Hong
H
Lee
Youn Soo
YS
Kim
Hae Joo
HJ
Jung
Sang Min
SM
Lee
Yu Sun
YS
Chung
Yeun Jun
YJ
Park
Yong Gyu
YG
Jung
Sang Seol
SS
Kim
Jin Woo
JW
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
D001057:Apolipoproteins E; C516325:HCCR1 protein, mouse; C476732:LETMD1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface