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

Authors :
Yoneda, Mitsuhiro
Suzuki, Toru
Nakamura, Takahisa
Ajima, Rieko
Yoshida, Yutaka
Kakuta, Shigeru
Sudo, Katsuko
Iwakura, Yoichiro
Shibutani, Makoto
Mitsumori, Kunitoshi
Yokota, Jun
Yamamoto, Tadashi
Source :
Cancer Science; Feb2009, Vol. 100 Issue 2, p225-232, 8p, 1 Color Photograph, 1 Chart, 4 Graphs
Publication Year :
2009

Abstract

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<superscript>−/–</superscript>) 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. ( Cancer Sci 2009; 100: 225–232) [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13479032
Volume :
100
Issue :
2
Database :
Complementary Index
Journal :
Cancer Science
Publication Type :
Academic Journal
Accession number :
36142720
Full Text :
https://doi.org/10.1111/j.1349-7006.2008.01030.x