| RRC ID |
37740
|
| Author |
Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y, Kakuta S, Katsuko S, Iwakura Y, Shibutani M, Mitsumori K, Yokota J, Yamamoto T.
|
| Title |
Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma.
|
| Journal |
Cancer Sci
|
| 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−/–) 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.
|
| Volume |
100(2)
|
| Pages |
225-32
|
| Published |
2009-2-1
|
| DOI |
10.1111/j.1349-7006.2008.01030.x
|
| PII |
CAS1030
|
| PMID |
19068083
|
| MeSH |
Adenocarcinoma / genetics
Adenocarcinoma / metabolism*
Adenocarcinoma / pathology*
Adult
Aged
Aged, 80 and over
Animals
Cell Cycle Proteins
Cell Proliferation
Female
Humans
Lung / metabolism
Lung / pathology
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Male
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
NIH 3T3 Cells
Plasminogen Activator Inhibitor 1 / genetics
Plasminogen Activator Inhibitor 1 / metabolism
Proteins / genetics
Proteins / metabolism*
Proteins / physiology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
4.966
|
| Times Cited |
39
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
Lu-134
Lu-135'(RCB0468)
Lu-139(RCB0469) |
