Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer

被引：93

作者：

Iwanaga, Kentaro ^{[1
]}

Yang, Yanan ^{[1
]}

Raso, Maria Gabriela ^{[1
,2
]}

Ma, Lijiang ^{[1
]}

Hanna, Amy E. ^{[1
]}

Thilaganathan, Nishan ^{[1
]}

Moghaddam, Seyed ^{[3
]}

Evans, Christopher M. ^{[3
]}

Li, Huaignang ^{[4
]}

Cai, Wei-Wen ^{[5
]}

Sato, Mitsuo ^{[7
]}

Minna, John D. ^{[7
]}

Wu, Hong ^{[8
]}

Creighton, Chad J. ^{[6
]}

Demayo, Francesco J. ^{[3
,4
]}

Wistuba, Ignacio I. ^{[1
,2
]}

Kurie, Jonathan M. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX USA

[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[5] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[6] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[7] Univ Texas SW Med Ctr Dallas, Harold Simmons Canc Ctr, Dallas, TX USA

[8] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA

来源：

CANCER RESEARCH | 2008年 / 68卷 / 04期

关键词：

D O I：

10.1158/0008-5472.CAN-07-3117

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non-small cell lung cancer cells, but the role of Pten in lung neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate Pten in the bronchial epithelium of mice. Although, by itself, Pten inactivation had no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median duration of survival, respectively). Lung tumors arose in K-ras mutant, Pten-deficient mice that rapidly obstructed bronchial lumina and replaced alveolar spaces. Relative to K-ras mutant tumors, the K-ras mutant, Pten-deficient tumors exhibited more advanced histologic severity and more prominent inflammation and vascularity. Thus, Pten inactivation cooperated with oncogenic K-ras in promoting lung tumorigenesis.

引用

页码：1119 / 1127

页数：9

共 52 条

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