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Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma.

Publication ,  Journal Article
Okamoto, T; Mandai, M; Matsumura, N; Yamaguchi, K; Kondoh, H; Amano, Y; Baba, T; Hamanishi, J; Abiko, K; Kosaka, K; Murphy, SK; Mori, S; Konishi, I
Published in: Mol Carcinog
January 2015

Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas that often arises in ovarian endometriosis. We previously reported that a unique carcinogenic environment, especially iron-induced oxidative stress in endometriotic cysts may promote development of OCCC. We also identified a gene expression profile characteristic of OCCC (the "OCCC signature"). This 320-gene OCCC signature is enriched in genes associated with stress response and sugar metabolism. However, the biological implication of this profile is unclear. In this study, we have focused on the biological role of the HNF-1β gene within the OCCC signature, which was previously shown to be overexpressed in OCCC. Suppression of HNF-1β in the HNF-1β-overexpressing human ovarian cancer cell line RMG2 using short hairpin RNA resulted in a significant increase in proliferation. It also facilitated glucose uptake, glycolytic activity, and lactate secretion along with increased expression of the glucose transporter-1 (GLUT-1) gene and several key enzymes in the glycolytic process. Conversely, forced expression of HNF-1β in the serous ovarian cancer cell line, Hey, resulted in slowed cellular growth and repressed glycolytic activity. These data suggest that HNF-1β represses cell growth, and at the same time, it promotes aerobic glycolysis which is known as the "Warburg effect." As the Warburg effect is regarded as a characteristic metabolic process in cancer which may contribute to cell survival under hypoxic conditions or in a stressful environment, overexpression of HNF-1β may play an inevitable role in the occurrence of OCCC in stressful environment.

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

January 2015

Volume

54

Issue

1

Start / End Page

35 / 49

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Hepatocyte Nuclear Factor 1-beta
  • Glycolysis
  • Glucose Transporter Type 1
  • Glucose
  • Gene Knockdown Techniques
  • Gene Expression Regulation, Neoplastic
  • Female
 

Citation

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Okamoto, T., Mandai, M., Matsumura, N., Yamaguchi, K., Kondoh, H., Amano, Y., … Konishi, I. (2015). Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma. Mol Carcinog, 54(1), 35–49. https://doi.org/10.1002/mc.22072
Okamoto, Takako, Masaki Mandai, Noriomi Matsumura, Ken Yamaguchi, Hiroshi Kondoh, Yasuaki Amano, Tsukasa Baba, et al. “Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma.Mol Carcinog 54, no. 1 (January 2015): 35–49. https://doi.org/10.1002/mc.22072.
Okamoto T, Mandai M, Matsumura N, Yamaguchi K, Kondoh H, Amano Y, et al. Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma. Mol Carcinog. 2015 Jan;54(1):35–49.
Okamoto, Takako, et al. “Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma.Mol Carcinog, vol. 54, no. 1, Jan. 2015, pp. 35–49. Pubmed, doi:10.1002/mc.22072.
Okamoto T, Mandai M, Matsumura N, Yamaguchi K, Kondoh H, Amano Y, Baba T, Hamanishi J, Abiko K, Kosaka K, Murphy SK, Mori S, Konishi I. Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma. Mol Carcinog. 2015 Jan;54(1):35–49.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

January 2015

Volume

54

Issue

1

Start / End Page

35 / 49

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Hepatocyte Nuclear Factor 1-beta
  • Glycolysis
  • Glucose Transporter Type 1
  • Glucose
  • Gene Knockdown Techniques
  • Gene Expression Regulation, Neoplastic
  • Female