Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer: Clinical significance

Masaaki Iwatsuki, Koshi Mimori, Hideshi Lshii, Takehiko Yokobori, Yasushi Takatsuno, Tetsuya Sato, Hiroyuki Toh, Ichiro Onoyama, Keiichi I. Nakayama, Hideo Baba, Masaki Mori

研究成果: ジャーナルへの寄稿学術誌査読

119 被引用数 (Scopus)

抄録

This study focused on a cell cycle regulatory gene, FBXW7, which ubiquitinates c-Myc and cyclin E and promotes exit from the cell cycle. We determined the expression level of FBXW7 in colorectal cancer (CRC) cases, correlated those values with clinicopathologic features, and characterized the molecular mechanism of reduced expression of FBXW7 in CRC cells in vitro. FBXW7 mRNA and protein expression were evaluated in 93 CRC cases. Using CGH array, the copy number aberrations of the flanking region of FBXW7 were evaluated in another 130 CRC specimens. In vitro analysis of FBXW7 gene silencing in CRC cells was conducted. FBXW7 mRNA expression was significantly tower in tumor tissues than the corresponding normal tissues. The low FBXW7 expression group showed a significantly poorer prognosis than patients in the high expression group. A concordant relationship was observed between the incidence of KXIRH repression and the genetic alteration. The incidence of genetic alteration was associated with the stage of disease progression. In vitro, FBXW7-specific siRNA enhanced expression of c-MYC and cyclin E proteins and up-regulated cell proliferation. Genetic alterations in tumors led to the loss of FBXW7 expression and increased cell proliferation. FBXW7 expression provides a prognostic factor for patients with CRC.

本文言語英語
ページ(範囲)1828-1837
ページ数10
ジャーナルInternational Journal of Cancer
126
8
DOI
出版ステータス出版済み - 4月 15 2010

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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