Role of GLI2 in the growth of human osteosarcoma

Hiroko Nagao, Kosei Ijiri, Masataka Hirotsu, Yasuhiro Ishidou, Takuya Yamamoto, Satoshi Nagano, Takumi Takizawa, Kinichi Nakashima, Setsuro Komiya, Takao Setoguchi

研究成果: ジャーナルへの寄稿学術誌査読

54 被引用数 (Scopus)

抄録

The Hedgehog pathway functions as an organizer in embryonic development. Aberrant activation of the Hedgehog pathway has been reported in various types of malignant tumours. The GLI2 transcription factor is a key mediator of Hedgehog pathway but its contribution to neoplasia is poorly understood. To establish the role of GLI2 in osteosarcoma, we examined its expression by real-time PCR using biopsy tissues. To examine the function of GLI2, we evaluated the growth of osteosarcoma cells and their cell cycle after GLI2 knockdown. To study the effect of GLI2 activation, we examined mesenchymal stem cell growth and the cell cycle after forced expression of GLI2. We found that GLI2 was aberrantly over-expressed in human osteosarcoma biopsy specimens. GLI2 knockdown by RNA interferences prevented osteosarcoma growth and anchorage-independent growth. Knockdown of GLI2 promoted the arrest of osteosarcoma cells in G1 phase and was accompanied by reduced protein expression of the cell cycle accelerators cyclin D1, SKP2 and phosphorylated Rb. On the other hand, knockdown of GLI2 increased the expression of p21 cip1. In addition, over-expression of GLI2 promoted mesenchymal stem cell proliferation and accelerated their cell cycle progression. Finally, evaluation of mouse xenograft models showed that GLI2 knockdown inhibited the growth of osteosarcoma in nude mice. Our findings suggest that inhibition of GLI2 may represent an effective therapeutic approach for patients with osteosarcoma.

本文言語英語
ページ(範囲)169-179
ページ数11
ジャーナルJournal of Pathology
224
2
DOI
出版ステータス出版済み - 6月 2011
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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