*From the Departments of Pathology (Drs. Morris, David, Fermin, and Brody, and Ms. Notwick) and Medicine (Dr. Friedman), Program in Lung Biology, Tulane University Medical Center, New Orleans, LA.
Correspondence to: Gilbert F. Morris, PhD, Department of Pathology, SL-79, Tulane University Medical Center, 1430 Tulane Ave, New Orleans, LA 70112; e-mail: email@example.com
The gene encoding the p53 tumor suppressor protein is commonly mutated in many human cancers, including lung cancer,1but p53 mutations are relatively rare in murine lung tumors induced by carcinogen exposures.2To model the pathogenesis of human lung cancers in mice, we disrupted wild-type p53 activities by transgenically expressing a dominant-negative form of p53 specifically in the lung epithelium using the human surfactant protein C (SPC) promoter, SPC-DNp53 mice.3Distinct responses to fibrogenic agents have indicated that the transgene has altered the phenotype of SPC-DNp53 mice.4However, the low incidence and delayed onset of lung tumor development in unexposed SPC-DNp53 mice imply that the oncogenic p53 transgene requires additional activities to complete the process of neoplastic conversion. Inhaled asbestos activates p53 expression at the sites of fiber deposition,5and epidemiologic evidence indicates that exposure to asbestos increases the risk of lung cancer about fivefold.6 We postulate that the p53-mediated response to asbestos protects against the development of lung tumors. In accord with this postulate, a single exposure to an aerosol of asbestos for 5 h produced a significantly higher incidence of lung tumors in SPC-DNp53 transgenic mice than in simultaneously exposed nontransgenic littermates. These data indicate that compromised p53 function in the lung epithelium cooperates with asbestos in lung tumorigenesis.
Abbreviation: SPC = surfactant protein C
This research was supported by the Louisiana Health Excellence Fund.
Become a CHEST member and receive a FREE subscription as a benefit of membership.
Individuals can purchase this article on ScienceDirect.
Individuals can purchase a subscription to the journal.
Individuals can purchase a subscription to the journal or buy individual articles.
Learn more about membership or Purchase a Full Subscription.
Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 7
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.