Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies. BMC Cancer 2005 Dec 06;5:155
Date
12/08/2005Pubmed ID
16332260Pubmed Central ID
PMC1325242DOI
10.1186/1471-2407-5-155Scopus ID
2-s2.0-29244445792 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Tichelaar JW, Zhang Y, leRiche JC, Biddinger PW, Lam S, Anderson MWMESH terms used to index this publication - Major topics in bold
ApoptosisBiopsy
Carcinoma in Situ
Carcinoma, Non-Small-Cell Lung
Cell Survival
Humans
Immunohistochemistry
Inhibitor of Apoptosis Proteins
Lung Neoplasms
Neoplasm Invasiveness
Oncogene Protein v-akt
Signal Transduction
Transcription Factor RelA
