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

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)225-232
Number of pages8
JournalCancer Science
Issue number2
Publication statusPublished - 2009


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