Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer

Jun Wang, Ali Shidfar, David Ivancic, Manish Ranjan, Liannian Liu, Mi Ran Choi, Vamsi Parimi, Demirkan Besim Gursel, Megan E. Sullivan, Matthew S. Najor, Abde M. Abukhdeir, Denise M Scholtens, Seema Ahsan Khan*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Risk biomarkers for estrogen receptor (ER)-negative breast cancer have clear value for breast cancer prevention. We previously reported a set of lipid metabolism (LiMe) genes with high expression in the contralateral unaffected breasts (CUBs) of ER-negative cancer cases. We now further examine LiMe gene expression in both tumor and CUB, and investigate the role of Pre-B-cell leukemia homeobox-1 (PBX1) as a candidate common transcription factor for LiMe gene expression. mRNA was extracted from laser-capture microdissected epithelium from tumor and CUB of 84 subjects (28 ER-positive cases, 28 ER-negative cases, 28 healthy controls). Gene expression was quantitated by qRT-PCR. Logistic regression models were generated to predict ER status of the contralateral cancer. Protein expression of HMGCS2 and PBX1 was measured using immunohistochemistry. The effect of PBX1 on LiMe gene expression was examined by overexpressing PBX1 in MCF10A cells with or without ER, and by suppressing PBX1 in MDA-MB-453 cells. The expression of DHRS2, HMGCS2, UGT2B7, UGT2B11, ALOX15B, HPGD, UGT2B28 and GLYATL1 was significantly higher in ER-negative versus ER-positive CUBs, and predicted ER status of the tumor in test and validation sets. In contrast, LiMe gene expression was significantly lower in ER-negative than ER-positive tumors. PBX1 overexpression in MCF10A cells up-regulated most LiMe genes, but not in MCF10A cells overexpressing ER. Suppressing PBX1 in MDA-MB-453 cells resulted in decrease of LiMe gene expression. Four binding sites of PBX1 and cofactor were identified in three lipid metabolism genes using ChIP-qPCR. These data suggest a novel role for PBX1 in the regulation of lipid metabolism genes in benign breast, which may contribute to ER-negative tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2484-2497
Number of pages14
JournalInternational Journal of Cancer
Volume140
Issue number11
DOIs
StatePublished - Jun 1 2017

Fingerprint

Lipid Metabolism
Estrogen Receptors
Breast
Breast Neoplasms
Genes
Gene Expression
Neoplasms
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Logistic Models
Homeobox Genes
Carcinogenesis
Lasers
Transcription Factors
Epithelium
Biomarkers
Immunohistochemistry
Binding Sites

Keywords

  • PBX1
  • contralateral breast
  • estrogen receptor
  • lipid metabolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wang, Jun ; Shidfar, Ali ; Ivancic, David ; Ranjan, Manish ; Liu, Liannian ; Choi, Mi Ran ; Parimi, Vamsi ; Gursel, Demirkan Besim ; Sullivan, Megan E. ; Najor, Matthew S. ; Abukhdeir, Abde M. ; Scholtens, Denise M ; Khan, Seema Ahsan. / Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer. In: International Journal of Cancer. 2017 ; Vol. 140, No. 11. pp. 2484-2497.
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abstract = "Risk biomarkers for estrogen receptor (ER)-negative breast cancer have clear value for breast cancer prevention. We previously reported a set of lipid metabolism (LiMe) genes with high expression in the contralateral unaffected breasts (CUBs) of ER-negative cancer cases. We now further examine LiMe gene expression in both tumor and CUB, and investigate the role of Pre-B-cell leukemia homeobox-1 (PBX1) as a candidate common transcription factor for LiMe gene expression. mRNA was extracted from laser-capture microdissected epithelium from tumor and CUB of 84 subjects (28 ER-positive cases, 28 ER-negative cases, 28 healthy controls). Gene expression was quantitated by qRT-PCR. Logistic regression models were generated to predict ER status of the contralateral cancer. Protein expression of HMGCS2 and PBX1 was measured using immunohistochemistry. The effect of PBX1 on LiMe gene expression was examined by overexpressing PBX1 in MCF10A cells with or without ER, and by suppressing PBX1 in MDA-MB-453 cells. The expression of DHRS2, HMGCS2, UGT2B7, UGT2B11, ALOX15B, HPGD, UGT2B28 and GLYATL1 was significantly higher in ER-negative versus ER-positive CUBs, and predicted ER status of the tumor in test and validation sets. In contrast, LiMe gene expression was significantly lower in ER-negative than ER-positive tumors. PBX1 overexpression in MCF10A cells up-regulated most LiMe genes, but not in MCF10A cells overexpressing ER. Suppressing PBX1 in MDA-MB-453 cells resulted in decrease of LiMe gene expression. Four binding sites of PBX1 and cofactor were identified in three lipid metabolism genes using ChIP-qPCR. These data suggest a novel role for PBX1 in the regulation of lipid metabolism genes in benign breast, which may contribute to ER-negative tumorigenesis.",
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Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer. / Wang, Jun; Shidfar, Ali; Ivancic, David; Ranjan, Manish; Liu, Liannian; Choi, Mi Ran; Parimi, Vamsi; Gursel, Demirkan Besim; Sullivan, Megan E.; Najor, Matthew S.; Abukhdeir, Abde M.; Scholtens, Denise M; Khan, Seema Ahsan.

In: International Journal of Cancer, Vol. 140, No. 11, 01.06.2017, p. 2484-2497.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer

AU - Wang, Jun

AU - Shidfar, Ali

AU - Ivancic, David

AU - Ranjan, Manish

AU - Liu, Liannian

AU - Choi, Mi Ran

AU - Parimi, Vamsi

AU - Gursel, Demirkan Besim

AU - Sullivan, Megan E.

AU - Najor, Matthew S.

AU - Abukhdeir, Abde M.

AU - Scholtens, Denise M

AU - Khan, Seema Ahsan

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Y1 - 2017/6/1

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AB - Risk biomarkers for estrogen receptor (ER)-negative breast cancer have clear value for breast cancer prevention. We previously reported a set of lipid metabolism (LiMe) genes with high expression in the contralateral unaffected breasts (CUBs) of ER-negative cancer cases. We now further examine LiMe gene expression in both tumor and CUB, and investigate the role of Pre-B-cell leukemia homeobox-1 (PBX1) as a candidate common transcription factor for LiMe gene expression. mRNA was extracted from laser-capture microdissected epithelium from tumor and CUB of 84 subjects (28 ER-positive cases, 28 ER-negative cases, 28 healthy controls). Gene expression was quantitated by qRT-PCR. Logistic regression models were generated to predict ER status of the contralateral cancer. Protein expression of HMGCS2 and PBX1 was measured using immunohistochemistry. The effect of PBX1 on LiMe gene expression was examined by overexpressing PBX1 in MCF10A cells with or without ER, and by suppressing PBX1 in MDA-MB-453 cells. The expression of DHRS2, HMGCS2, UGT2B7, UGT2B11, ALOX15B, HPGD, UGT2B28 and GLYATL1 was significantly higher in ER-negative versus ER-positive CUBs, and predicted ER status of the tumor in test and validation sets. In contrast, LiMe gene expression was significantly lower in ER-negative than ER-positive tumors. PBX1 overexpression in MCF10A cells up-regulated most LiMe genes, but not in MCF10A cells overexpressing ER. Suppressing PBX1 in MDA-MB-453 cells resulted in decrease of LiMe gene expression. Four binding sites of PBX1 and cofactor were identified in three lipid metabolism genes using ChIP-qPCR. These data suggest a novel role for PBX1 in the regulation of lipid metabolism genes in benign breast, which may contribute to ER-negative tumorigenesis.

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KW - estrogen receptor

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