Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies.
BACKGROUND
The development of non-small cell lung carcinoma proceeds through a series of well-defined pathological steps before the appearance of invasive lung carcinoma. The molecular changes that correspond with pathology changes are not well defined and identification of the molecular events may provide clues on the progression of intraepithelial neoplasia in the lung, as well as suggest potential targets for chemoprevention. The acquisition of anti-apoptotic signals is critical for the survival of cancer cells but the pathways involved are incompletely characterized in developing intra-epithelial neoplasia (IEN).


METHODS
We used immunohistochemistry to determine the presence, relative levels, and localization of proteins that mediate anti-apoptotic pathways in developing human bronchial neoplasia.


RESULTS
Bronchial epithelial protein levels of the phosphorylated (active) form of AKT kinase and the caspase inhibitor cIAP-2 were increased in more advanced grades of bronchial IEN lesions than in normal bronchial epithelium. Additionally, the percentage of biopsies with nuclear localization of p65/RELA in epithelial cells increased with advancing pathology grade, suggesting that NF-kappaB transcriptional activity was induced more frequently in advanced IEN lesions.


CONCLUSIONS
Our results indicate that anti-apoptotic pathways are elevated in bronchial IEN lesions prior to the onset of invasive carcinoma and that targeting these pathways therapeutically may offer promise in prevention of non-small cell lung carcinoma.
Tichelaar
Jay W
JW
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Jay.Tichelaar@uc.edu
Zhang
Yu
Y
leRiche
Jean C
JC
Biddinger
Paul W
PW
Lam
Stephen
S
Anderson
Marshall W
MW
D017209:Apoptosis; D001706:Biopsy; D002278:Carcinoma in Situ / Q000235:genetics* / Q000503:physiopathology; D002289:Carcinoma, Non-Small-Cell Lung; D002470:Cell Survival; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis* / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000032:analysis* / Q000096:biosynthesis; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000032:analysis* / Q000096:biosynthesis
D051034:Inhibitor of Apoptosis Proteins; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051058:Oncogene Protein v-akt