Expression of TGFbeta type-II receptor in association with markers of proliferation and apoptosis in premalignant lung lesions.
BACKGROUND
Analysis of the early molecular abnormalities that play an oncogenic role in the progression of pulmonary neoplasia may lead to the identification of useful markers for early detection and prognosis. In normal squamous epithelium, transforming growth factor beta (TGFbeta) regulates cell growth and differentiation via specific membranous receptors and intracellular signaling molecules (Smads). The authors previously observed that, in head and neck squamous cell carcinoma, the expression of the TGFbeta type II receptor (TbetaR-II) decreases as tumors become less differentiated and more biologically aggressive.


METHODS
In this pilot study of 48 premalignant bronchoepithelial lesions, the authors evaluated the expression of TbetaR-II and 2 proliferation markers (Ki-67 and MCM2), and the amount of early DNA fragmentation as evidence of apoptosis.


RESULTS
The authors observed that the progression of premalignant lesions toward carcinoma in situ is accompanied by a decrease in TBR II expression and apoptosis and an increase in the expression of Ki-67 and MCM2.


CONCLUSIONS
These results suggested that the TGFbeta pathway may be impaired early in the neoplastic process and that a combination of selected markers can provide a useful profile to detect preneoplastic changes in individuals at high risk for developing pulmonary carcinoma.
Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Teresita
T
Muñoz-Antonia
Carlos
C
Muro-Cacho
Swati
S
Sharma
Alan
A
Cantor
Gerold
G
Bepler
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis; D049109:Cell Proliferation; D053938:DNA Fragmentation; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008679:Metaplasia / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000032:analysis; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2