Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma

Mitsuhiro Yoneda, Toru Suzuki, Takahisa Nakamura, Rieko Ajima, Yutaka Yoshida, Shigeru Kakuta, Katsuko Sudo, Yoichiro Iwakura, Makoto Shibutani, Kunitoshi Mitsumori, Jun Yokota, Tadashi Yamamoto

研究成果: Article

38 引用 (Scopus)

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The abundant in neuroepithelium area (ana) gene was originally identified as a member of the tob/btg family of antiproliferative genes. Like the other family members, Ana inhibits growth of NIH3T3 cells when overexpressed. However, whether or not Ana is involved in tumor progression has been elusive. Here, we show that expression of ana is relatively high in the lung, the expression being restricted in type II alveolar epithelial cells. We further show that ana expression is reduced in 97% of the human lung cancer cell lines examined (61/63) and 86% of clinical samples from lung adenocarcinoma patients (36/42). Long-term observation of ana-deficient (ana-/-) mice reveals that 8% of them develop lung tumors (5/66) by 21 months after birth, while 0% of wild-type mice (0/35) develop the same type of tumors. We also show that exogenously expressed ana gene product suppresses the levels of matrix metalloproteinase-2 (MMP-2) and plasminogen activator inhibitor-1 (PAI-1) expression in lung cancer cells. Taken together, we propose that ana functions as a tumor suppressor and that its product inhibits tumor progression as well by suppressing angiogenesis, invasion, and metastasis.

元の言語English
ページ(範囲)225-232
ページ数8
ジャーナルCancer science
100
発行部数2
DOI
出版物ステータスPublished - 2009 1 28
外部発表Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yoneda, M., Suzuki, T., Nakamura, T., Ajima, R., Yoshida, Y., Kakuta, S., Sudo, K., Iwakura, Y., Shibutani, M., Mitsumori, K., Yokota, J., & Yamamoto, T. (2009). Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma. Cancer science, 100(2), 225-232. https://doi.org/10.1111/j.1349-7006.2008.01030.x