論文

査読有り 国際誌
2017年5月

Inverse relationship between insulin receptor expression and progression in renal cell carcinoma.

Oncology reports
  • Makoto Takahashi
  • ,
  • Takamitsu Inoue
  • ,
  • Mingguo Huang
  • ,
  • Kazuyuki Numakura
  • ,
  • Hiroshi Tsuruta
  • ,
  • Mitsuru Saito
  • ,
  • Atsushi Maeno
  • ,
  • Eijiro Nakamura
  • ,
  • Shintaro Narita
  • ,
  • Norihiko Tsuchiya
  • ,
  • Tomonori Habuchi

37
5
開始ページ
2929
終了ページ
2941
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/or.2017.5552

We investigated the relationship among serum insulin level, insulin receptor (IR) expression in renal cell carcinoma (RCC), and outcomes in patients with RCC who underwent nephrectomy. We also explored the role of insulin signaling in RCC progression in a murine RCC allograft RENCA model using metformin to treat hyperinsulinemia induced by a high-carbohydrate diet. Clinically, the IR expression level in RCC tissue was significantly lower in patients with tumor stage pT2-4 and/or distant metastases. The IR expression level in RCC tissue was significantly lower in patients with preoperative serum C-peptide levels greater than or equal to the median than in patients with levels less than the median. High IR expression level was significantly associated with better disease-free and overall survival after nephrectomy. The IR expression level was significantly higher in murine subcutaneous flank tumors of the low-carbohydrate diet group and high-carbohydrate diet plus metformin group than of the high‑carbohydrate diet group. In vivo progression of murine tumors was not significantly enhanced by hyperinsulinemia induced by a high-carbohydrate diet and was significantly inhibited by metformin in both the low- and high‑carbohydrate diet groups. IR expression in RCC tissue was inversely associated with cancer progression in the clinical and murine experimental model studies. The clinical and murine allograft model study results suggested that hyperinsulinemia does not promote RCC progression. Decreased IR expression in high‑stage RCC tumors with poor prognosis may be the result of downregulation induced by the host's hyperinsulinemia.

リンク情報
DOI
https://doi.org/10.3892/or.2017.5552
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28393204

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