The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies

Michihiko Kuwano, Takeshi Uchiumi, Hiroshi Hayakawa, Mayumi Ono, Morimasa Wada, Hiroto Izumi, Kimitoshi Kohno

研究成果: Contribution to journalReview article査読

抄録

In our laboratories, we have been studying molecular targets which might be advantageous for novel cancer therapeutics. In this review, we focus on how ATP-binding cassette (ABC) transporter superfamily genes, Y-box-binding protein-1 (YB-1), and tumor angiogenesis-associated factors could contribute to the development of novel strategies for molecular cancer therapeutics. ABC transporters such as P-glycoprotein/MDR1 and several MRP family proteins function to protect cells from xenobiotics, drugs and poisons, suggesting that ABC transporters are a double-edged sword. In this regard, P-glycoprotein/MDR1 is a representative ABC transporter which plays a critical role in the efflux of a wide range of drugs. We have reported that gene amplification, gene rearrangements, transcription factor YB-1 and CpG methylation on the promoter are involved in MDR1 gene overexpression in cultured cancer cells. Among them, two mechanisms appear to be relevant to the up-regulation of MDR1 gene in human malignancies. We first reported that MDR1 gene promoter is activated in response to environmental stimuli, and is modulated by methylation/demethylation of CpG sites on the MDR1 promoter. We also demonstrated that YB-1 modulates not only transcription of various genes associated with cell growth, drug resistance and DNA synthesis, but also translation, mRNA stabilization and DNA repair/self-defense processes. Angiogenesis is also involved in tumor growth, invasion and metastasis of various malignancies, and so angiogenesis-related molecules also offer novel molecular targets for anticancer therapeutics.

本文言語英語
ページ(範囲)247-259
ページ数13
ジャーナルGann Monographs on Cancer Research
52
出版ステータス出版済み - 7 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • Cancer Research

フィンガープリント 「The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル