Open AccessDeficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma
Author(s) -
Yoneda Mitsuhiro,
Suzuki Toru,
Nakamura Takahisa,
Ajima Rieko,
Yoshida Yutaka,
Kakuta Shigeru,
Sudo Katsuko,
Iwakura Yoichiro,
Shibutani Makoto,
Mitsumori Kunitoshi,
Yokota Jun,
Yamamoto Tadashi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01030.x
Subject(s) - lung cancer , cancer research , plasminogen activator , adenocarcinoma , metastasis , biology , angiogenesis , lung , gene product , plasminogen activator inhibitor 1 , cancer , pathology , gene expression , gene , medicine , endocrinology , genetics
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. ( Cancer Sci 2009; 100: 225–232)