Abstract
Expression of the HER2 oncogene is increased in ∼30% of human breast carcinomas and is closely correlated with the expression of fatty acid synthase (FASN). In the present study, we determined the mechanism by which FASN and acetyl-CoA carboxylase α (ACCα) could be induced by HER2 overexpression. SK-BR-3 and BT-474 cells, breast cancer cells that overexpress HER2, expressed higher levels of FASN and ACCα compared with MCF-7 and MDA-MB-231 breast cancer cells in which HER2 expression is low. The induction of FASN and ACCα in BT474 cells were not mediated by the activation of SREBP-1. Exogenous HER2 expression in MDA-MB-231 cells induced the expression of FASN and ACCα, and the HER2-mediated increase in ACCα and FASN was inhibited by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. In addition, the activation of mTOR by the overexpression of RHEB in MDA-MB-231 cells increased the synthetic rates of both FASN and ACCα. On the other hand, FASN and ACCα were reduced in BT-474 cells by a blockade of the mTOR signaling pathway. These changes observed in their protein levels were not accompanied by changes in their mRNA levels. The 5′-and 3′-untranslated regions of both FASN and ACCα mRNAs were involved in selective translational induction that was mediated by mTOR signal transduction. These results strongly suggest that the major mechanism of HER2-mediated induction of FASN and ACCα in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 26122-26131 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 36 |
| DOIs | |
| Publication status | Published - 2007 Sep 7 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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Up-regulation of acetyl-CoA carboxylase α and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells. / Yoon, Sarah; Lee, Min Young; Park, Sahng Wook; Moon, Jong Seok; Koh, Yoo Kyung; Ahn, Yong Ho; Park, Byeong Woo; Kim, Kyung Sup.
In: Journal of Biological Chemistry, Vol. 282, No. 36, 07.09.2007, p. 26122-26131.Research output: Contribution to journal › Article
TY - JOUR
T1 - Up-regulation of acetyl-CoA carboxylase α and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells
AU - Yoon, Sarah
AU - Lee, Min Young
AU - Park, Sahng Wook
AU - Moon, Jong Seok
AU - Koh, Yoo Kyung
AU - Ahn, Yong Ho
AU - Park, Byeong Woo
AU - Kim, Kyung Sup
PY - 2007/9/7
Y1 - 2007/9/7
N2 - Expression of the HER2 oncogene is increased in ∼30% of human breast carcinomas and is closely correlated with the expression of fatty acid synthase (FASN). In the present study, we determined the mechanism by which FASN and acetyl-CoA carboxylase α (ACCα) could be induced by HER2 overexpression. SK-BR-3 and BT-474 cells, breast cancer cells that overexpress HER2, expressed higher levels of FASN and ACCα compared with MCF-7 and MDA-MB-231 breast cancer cells in which HER2 expression is low. The induction of FASN and ACCα in BT474 cells were not mediated by the activation of SREBP-1. Exogenous HER2 expression in MDA-MB-231 cells induced the expression of FASN and ACCα, and the HER2-mediated increase in ACCα and FASN was inhibited by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. In addition, the activation of mTOR by the overexpression of RHEB in MDA-MB-231 cells increased the synthetic rates of both FASN and ACCα. On the other hand, FASN and ACCα were reduced in BT-474 cells by a blockade of the mTOR signaling pathway. These changes observed in their protein levels were not accompanied by changes in their mRNA levels. The 5′-and 3′-untranslated regions of both FASN and ACCα mRNAs were involved in selective translational induction that was mediated by mTOR signal transduction. These results strongly suggest that the major mechanism of HER2-mediated induction of FASN and ACCα in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway.
AB - Expression of the HER2 oncogene is increased in ∼30% of human breast carcinomas and is closely correlated with the expression of fatty acid synthase (FASN). In the present study, we determined the mechanism by which FASN and acetyl-CoA carboxylase α (ACCα) could be induced by HER2 overexpression. SK-BR-3 and BT-474 cells, breast cancer cells that overexpress HER2, expressed higher levels of FASN and ACCα compared with MCF-7 and MDA-MB-231 breast cancer cells in which HER2 expression is low. The induction of FASN and ACCα in BT474 cells were not mediated by the activation of SREBP-1. Exogenous HER2 expression in MDA-MB-231 cells induced the expression of FASN and ACCα, and the HER2-mediated increase in ACCα and FASN was inhibited by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. In addition, the activation of mTOR by the overexpression of RHEB in MDA-MB-231 cells increased the synthetic rates of both FASN and ACCα. On the other hand, FASN and ACCα were reduced in BT-474 cells by a blockade of the mTOR signaling pathway. These changes observed in their protein levels were not accompanied by changes in their mRNA levels. The 5′-and 3′-untranslated regions of both FASN and ACCα mRNAs were involved in selective translational induction that was mediated by mTOR signal transduction. These results strongly suggest that the major mechanism of HER2-mediated induction of FASN and ACCα in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway.
UR - http://www.scopus.com/inward/record.url?scp=34548814981&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548814981&partnerID=8YFLogxK
U2 - 10.1074/jbc.M702854200
DO - 10.1074/jbc.M702854200
M3 - Article
C2 - 17631500
AN - SCOPUS:34548814981
VL - 282
SP - 26122
EP - 26131
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 36
ER -