TY - JOUR
T1 - Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma
AU - Yoneda, Mitsuhiro
AU - Suzuki, Toru
AU - Nakamura, Takahisa
AU - Ajima, Rieko
AU - Yoshida, Yutaka
AU - Kakuta, Shigeru
AU - Sudo, Katsuko
AU - Iwakura, Yoichiro
AU - Shibutani, Makoto
AU - Mitsumori, Kunitoshi
AU - Yokota, Jun
AU - Yamamoto, Tadashi
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1349-7006.2008.01030.x
DO - 10.1111/j.1349-7006.2008.01030.x
M3 - Article
C2 - 19068083
AN - SCOPUS:58549084814
VL - 100
SP - 225
EP - 232
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 2
ER -