Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.
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 approximately 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.
Reisman
David N
DN
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599-7295, USA.
Sciarrotta
Janiece
J
Wang
Weidong
W
Funkhouser
William K
WK
Weissman
Bernard E
BE
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D004265:DNA Helicases; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency*; D011379:Prognosis; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency*; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases