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Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity.

Ha SA, Shin SM, Kim HK, Kim S, Namkoong H, Lee YS, Kim HJ, Jung SM, Lee YS, Chung YJ, Park YG, Jung SS, Kim JW - J. Cell. Mol. Med. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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.

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HCCR-1 and ApoE expressions in human tissues. (A, B) Northern analyses of HCCR-1 (A) and ApoE (B) in human breast tissues and cell lines. Comparison of HCCR-1 mRNA expressions in breast cancer cell lines (BT-474, MCF-7 and MDA-MB-231), and fresh primary breast cancer tissues (C) and their corresponding normal counterparts (N). Human β-actin cDNA was used as a control probe (bottom panel). (C, D) mRNA expression levels of ApoE in various normal human tissues and cancer cell lines. Northern-blots consisting of 8 human cancer cell lines (C) and 12 normal human tissues (D) were probed with radioactively labelled ApoE cDNA (top panel).
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fig01: HCCR-1 and ApoE expressions in human tissues. (A, B) Northern analyses of HCCR-1 (A) and ApoE (B) in human breast tissues and cell lines. Comparison of HCCR-1 mRNA expressions in breast cancer cell lines (BT-474, MCF-7 and MDA-MB-231), and fresh primary breast cancer tissues (C) and their corresponding normal counterparts (N). Human β-actin cDNA was used as a control probe (bottom panel). (C, D) mRNA expression levels of ApoE in various normal human tissues and cancer cell lines. Northern-blots consisting of 8 human cancer cell lines (C) and 12 normal human tissues (D) were probed with radioactively labelled ApoE cDNA (top panel).

Mentions: We examined the expression patterns of HCCR-1 or ApoE in human normal tissues, cancer tissues and cell lines. Northern blot analysis revealed an increased expression of HCCR-1 in primary human breast cancer tissues and breast cancer cell lines compared to normal breast tissues (Fig. 1A). In contrast to the overexpression of HCCR-1 in breast cancer tissues and cell lines, expression of ApoE was little or absent in breast cancer tissues and cell lines (Fig. 1B). Thus, the expression of ApoE and HCCR-1 seems to be opposite. We also examined the expression of ApoE in other cancer cell types. ApoE mRNA was not detected in promyelocytic leukaemia cell HL-60, human cervical cancer cell HeLa, chronic myelogenous leukaemia cells K562, lymphoblastic leukaemia cell MOLT-4, Burkitt’s lymphoma cell Raji, colon cancer cell SW480, lung cancer cell A549 and melanoma cell G361 (Fig. 1C). However, northern blot analysis with several normal tissues revealed that normal liver and kidney tissues have an abundant expression of ApoE among 12 normal tissues tested (Fig. 1D).


Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity.

Ha SA, Shin SM, Kim HK, Kim S, Namkoong H, Lee YS, Kim HJ, Jung SM, Lee YS, Chung YJ, Park YG, Jung SS, Kim JW - J. Cell. Mol. Med. (2009)

HCCR-1 and ApoE expressions in human tissues. (A, B) Northern analyses of HCCR-1 (A) and ApoE (B) in human breast tissues and cell lines. Comparison of HCCR-1 mRNA expressions in breast cancer cell lines (BT-474, MCF-7 and MDA-MB-231), and fresh primary breast cancer tissues (C) and their corresponding normal counterparts (N). Human β-actin cDNA was used as a control probe (bottom panel). (C, D) mRNA expression levels of ApoE in various normal human tissues and cancer cell lines. Northern-blots consisting of 8 human cancer cell lines (C) and 12 normal human tissues (D) were probed with radioactively labelled ApoE cDNA (top panel).
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Related In: Results  -  Collection

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fig01: HCCR-1 and ApoE expressions in human tissues. (A, B) Northern analyses of HCCR-1 (A) and ApoE (B) in human breast tissues and cell lines. Comparison of HCCR-1 mRNA expressions in breast cancer cell lines (BT-474, MCF-7 and MDA-MB-231), and fresh primary breast cancer tissues (C) and their corresponding normal counterparts (N). Human β-actin cDNA was used as a control probe (bottom panel). (C, D) mRNA expression levels of ApoE in various normal human tissues and cancer cell lines. Northern-blots consisting of 8 human cancer cell lines (C) and 12 normal human tissues (D) were probed with radioactively labelled ApoE cDNA (top panel).
Mentions: We examined the expression patterns of HCCR-1 or ApoE in human normal tissues, cancer tissues and cell lines. Northern blot analysis revealed an increased expression of HCCR-1 in primary human breast cancer tissues and breast cancer cell lines compared to normal breast tissues (Fig. 1A). In contrast to the overexpression of HCCR-1 in breast cancer tissues and cell lines, expression of ApoE was little or absent in breast cancer tissues and cell lines (Fig. 1B). Thus, the expression of ApoE and HCCR-1 seems to be opposite. We also examined the expression of ApoE in other cancer cell types. ApoE mRNA was not detected in promyelocytic leukaemia cell HL-60, human cervical cancer cell HeLa, chronic myelogenous leukaemia cells K562, lymphoblastic leukaemia cell MOLT-4, Burkitt’s lymphoma cell Raji, colon cancer cell SW480, lung cancer cell A549 and melanoma cell G361 (Fig. 1C). However, northern blot analysis with several normal tissues revealed that normal liver and kidney tissues have an abundant expression of ApoE among 12 normal tissues tested (Fig. 1D).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus