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[Cancer Research 63, 560-566, February 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Loss of BRG1/BRM in Human Lung Cancer Cell Lines and Primary Lung Cancers: Correlation with Poor Prognosis1

David N. Reisman2, Janiece Sciarrotta, Weidong Wang, William K. Funkhouser and Bernard E. Weissman3

Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525 [J. S., W. K. F., B. E. W.]; Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 [W. W.]; and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7295 [D. N. R., B. E. W.]

A role for the SWI/SNF complex in tumorigenesis based on its requirement for retinoblastoma induced growth arrest and p53-mediated transcription and the appearance of tumors in SWI/SNF-deficient mice. In addition, Western blot data have shown that the SWI/SNF ATPase subunits cell, BRG1 and BRM (BRG1/BRM), are lost in ~30% of human non-small lung cancer cell lines. To determine whether loss of expression of these proteins occurs in primary tumors, we examined their expression in 41 primary lung adenocarcinomas and 19 primary lung squamous carcinomas by immunohistochemistry. These analyses showed that 10% of tumors show a concomitant loss of BRG1 and BRM expression. Moreover, patients with BRG1/BRM-negative carcinomas, independent of stage, have a statistically significant decrease in survival compared with patients with BRG1/BRM. This report provides supportive evidence that BRG1 and BRM act as tumor suppressor proteins and implicates a role for their loss in the development of non-small cell lung cancers.




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