This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Macias-Perez, I. Articles by Pozzi, A. Search for Related Content PubMed PubMed Citation Articles by Macias-Perez, I. Articles by Pozzi, A.

Loss of Integrin 1β1 Ameliorates Kras-Induced Lung Cancer

Departments of ¹ Medicine (Division of Nephrology), ² Cancer Biology, and ³ Cell Biology, Vanderbilt University Medical Center, and ⁴ Department of Medicine, Veterans Affairs Hospital, Nashville, Tennessee

Requests for reprints: Ambra Pozzi, Department of Medicine, Division of Nephrology, Vanderbilt University, Medical Center North, B3115, Nashville, TN 37232. Phone: 615-322-4637; Fax: 615-322-4690; E-mail: ambra.pozzi{at}vanderbilt.edu.

Key Words: oncogenes • receptors • lung • cancer • initiation

The collagen IV binding receptor integrin 1β1 has been shown to regulate lung cancer due to its proangiogenic properties; however, it is unclear whether this receptor also plays a direct role in promoting primary lung tumors. To investigate this possibility, integrin 1-null mice were crossed with KrasLA2 mice that carry an oncogenic mutation of the Kras gene (G12D) and develop spontaneous primary tumors with features of non–small cell lung cancer. We provide evidence that KrasLA2/1-null mice have a decreased incidence of primary lung tumors and longer survival compared with KrasLA2/1 wild-type controls. Tumors from KrasLA2/1-null mice were also smaller, less vascularized, and exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen and terminal deoxynucleotidyl-transferase–mediated dUTP nick-end staining, respectively. Moreover, tumors from the KrasLA2/1-null mice showed diminished extracellular signal-regulated kinase (ERK) but enhanced p38 mitogen-activated protein kinase activation. Primary lung tumor epithelial cells isolated from KrasLA2/1-null mice showed a significant decrease in anchorage-independent colony formation, collagen-mediated cell proliferation, ERK activation, and, most importantly, tumorigenicity when injected into nude mice compared with KrasLA2/1 wild-type tumor cells. These results indicate that loss of the integrin 1 subunit decreases the incidence and growth of lung epithelial tumors initiated by oncogenic Kras, suggesting that both Kras and integrin 1β1 cooperate to drive the growth of non–small cell lung cancer in vivo. [Cancer Res 2008;68(15):6127–35]

This article has been cited by other articles:

				S. Dubey and C. A. Powell Update in Lung Cancer 2008 Am. J. Respir. Crit. Care Med., May 15, 2009; 179(10): 860 - 868. [Full Text] [PDF]