Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells.
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.
Maniwa
Yoshimasa
Y
Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshimura
Masahiro
M
Bermudez
Vladimir P
VP
Yuki
Takeshi
T
Okada
Kenji
K
Kanomata
Naoki
N
Ohbayashi
Chiho
C
Hayashi
Yoshitake
Y
Hurwitz
Jerard
J
Okita
Yutaka
Y
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D016022:Case-Control Studies; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000493:pharmacokinetics; D002467:Cell Nucleus / Q000737:chemistry; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; C069930:rad9 protein