Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies.

Abstract:

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. CONCLUSION: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.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Tichelaar JW,Zhang Y,leRiche JC,Biddinger PW,Lam S,Anderson MW

doi

10.1186/1471-2407-5-155

keywords:

subject

Has Abstract

pub_date

2005-12-06 00:00:00

pages

155

issn

1471-2407

pii

1471-2407-5-155

journal_volume

5

pub_type

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