Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells Journal Article


Authors: Maniwa, Y.; Yoshimura, M.; Bermudez, V. P.; Yuki, T.; Okada, K.; Kanomata, N.; Ohbayashi, C.; Hayashi, Y.; Hurwitz, J.; Okita, Y.
Article Title: Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells
Abstract: BACKGROUND. DNA damage sensor proteins have received much attention as upstream components of the DNA damage checkpoint signaling pathway that are required for cell cycle control and the induction of apoptosis. Deficiencies in these proteins are directly linked to the accumulation of gene mutations, which can induce cellular transformation and result in malignant disease. METHODS. Using 48 sets of tumor tissue specimens and peripheral normal lung tissue specimens from 48 patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the authors investigated the expression of hRad9 protein, a member of the human DNA damage sensor family, using immunohistochemical and Western blot analyses. RESULTS. Immunohistochemical analysis detected the accumulation of hRad9 in the nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue specimens examined). Western blot analysis also revealed elevated levels of phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection of phosphorylated Chk1, a protein kinase that regulates the downstream signaling of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was correlated with an increase in Ki-67 expression index in the tumor cells that were examined. CONCLUSIONS. The findings made in the current study suggest that Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype. © 2004 American Cancer Society.
Keywords: immunohistochemistry; adult; clinical article; controlled study; human tissue; protein phosphorylation; aged; middle aged; gene mutation; case-control studies; cancer staging; protein localization; ki 67 antigen; phenotype; cell cycle proteins; dna damage; cell cycle; gene overexpression; apoptosis; gene expression profiling; phosphatase; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; tumor cells, cultured; protein p53; cell transformation, neoplastic; blotting, western; western blotting; cell cycle checkpoint; cell nucleus; checkpoint kinase 1; phosphotransferase; p53; nonsmall cell lung carcinoma; labeling index; protein rad9; rad9
Journal Title: Cancer
Volume: 103
Issue: 1
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2005-01-01
Start Page: 126
End Page: 132
Language: English
DOI: 10.1002/cncr.20740
PUBMED: 15558813
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 21" - "Export Date: 24 October 2012" - "CODEN: CANCA" - "Source: Scopus"
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  1. Jerard Hurwitz
    206 Hurwitz