Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis

Seiichi Ishida, Yukari Shigemoto-Mogami, Youichi Shinozaki, Hiroyuki Kagechika, Koichi Shudo, Shogo Ozawa, Jun Ichi Sawada, Yasuo Ohno, Kazuhide Inoue

研究成果: Contribution to journalArticle査読

24 被引用数 (Scopus)

抄録

All-trans retinoic acid (ATRA) and Am80 are natural and synthetic derivatives of Vitamin A and have been used in the fields of oncology and dermatology for years. Their action was considered to be achieved mainly through binding to nuclear hormone receptors, retinoic acid receptors (RARs), although they have been observed to have different biological effects. For example, the two compounds have similar effects on differentiation but different effects on proliferation in human promyelocytic leukemia cell line HL-60 cells. To elucidate the genes responsible for this and other differences, we attempted for the first time to determine the genes whose expressions were differentially modulated during the time course of HL-60 cell differentiation by ATRA and Am80 treatment up to 72 h utilizing DNA microarray and clustering analyses. As a result, the expressions of 204 genes were found to be modulated differentially by ATRA and Am80. Among them, we focused on two components of the PI3-kinase/Akt signal transduction pathway, phosphoinositide-3-kinase, β-catalytic subunit and ribosomal protein S6 kinase polypeptide 1, which are related to the regulation of cell proliferation and apoptosis. Their expressions were specifically suppressed by ATRA, which coincided with the suppressive effects of ATRA on the HL-60 cell proliferation. Moreover, PI3-kinase inhibitors suppressed the proliferation of Am80-treated cells to the same extent as ATRA did. These results indicated that these gene products play a role in HL-60 cell growth suppression during the late stage of differentiation. The complete data and a list of the genes are available at http://www.nihs.go.jp/mpj/index-e.htm.

本文言語英語
ページ(範囲)2177-2186
ページ数10
ジャーナルBiochemical Pharmacology
68
11
DOI
出版ステータス出版済み - 12 1 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 薬理学

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