PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells

Hiromichi Yuki, Shikiko Ueno, Hiro Tatetsu, Hiroaki Niiro, Tadafumi Iino, Shinya Endo, Yawara Kawano, Yoshihiro Komohara, Motohiro Takeya, Hiroyuki Hata, Seiji Okada, Toshiki Watanabe, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno

研究成果: ジャーナルへの寄稿学術誌査読

35 被引用数 (Scopus)


PU.1 has previously been shown to be down-regulated in classical Hodgkin lymphoma (cHL) cells via promoter methylation. We performed bisulfite sequencing and proved that the promoter region and the -17 kb upstream regulatory element of the PU.1 gene were highly methylated. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we conditionally expressed PU.1 in 2 cHL cell lines, L428 and KM-H2. Overexpression of PU.1 induced complete growth arrest and apoptosis in both cell lines. Furthermore, in a Hodgkin lymphoma tumor xenograft model using L428 and KM-H2 cell lines, overexpression of PU.1 led to tumor regression or stable disease. Lentiviral transduction of PU.1 into primary cHL cells also induced apoptosis. DNA microarray analysis revealed that among genes related to cell cycle and apoptosis, p21 (CDKN1A) was highly up-regulated in L428 cells after PU.1 induction. Stable knockdown of p21 rescued PU.1-induced growth arrest in L428 cells, suggesting that the growth arrest and apoptosis observed are at least partially dependent on p21 up-regulation. These data strongly suggest that PU.1 is a potent tumor suppressor in cHL and that induction of PU.1 with demethylation agents and/or histone deacetylase inhibitors is worth exploring as a possible therapeutic option for patients with cHL.

出版ステータス出版済み - 2月 7 2013

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学


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