Format

Send to

Choose Destination
Clin Epigenetics. 2015 Jan 14;7:1. doi: 10.1186/s13148-014-0036-2. eCollection 2015.

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients.

Author information

1
Department of Life Science, National Chung Cheng University, 168 University Road, Min-Hsiung, Chia-Yi 621, Taiwan ; Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan ; Division of Gastroenterology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
2
Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, No 291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561 Taiwan.
3
Department of Life Science, National Chung Cheng University, 168 University Road, Min-Hsiung, Chia-Yi 621, Taiwan ; Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan.
4
Department of Life Science, National Chung Cheng University, 168 University Road, Min-Hsiung, Chia-Yi 621, Taiwan.
5
Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH USA.
6
Department of Life Science, Tunghai University, Taichung, Taiwan.
7
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
8
Medical Sciences, Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Bloomington, IN USA.
9
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX USA.
10
Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, No 291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561 Taiwan ; Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Clinical Pharmacology, Xiangya Hospital; Institute of Clinical Pharmacology, Central South University and Hunan Key Laboratory of Pharmacogenetics, Changsha, China.

Abstract

BACKGROUND:

The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation.

RESULTS:

We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038).

CONCLUSIONS:

ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients.

KEYWORDS:

ABCA1; Epigenetics; Ovarian cancer

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center