Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with telomere regulation, telomerase activity in human gastric carcinomas.
The MRE11 complex (MRE11, RAD50, NBS1) are required for the repair of DNA double-strand breaks and have another important function in regulating telomere length. The silent information regulator (Sir) proteins required for telomere position effect also bind telomeres. hRap1 protein is a human ortholog of yeast Rap1 which regulates telomere length by interacting with TRF2 and is recruited to telomeres by TRF2. We examined the expression of the MRE11 complex (MRE11, RAD50, NBS1), Sir2 and hRAP1 in 20 gastric carcinomas by reverse transcription polymerase chain reaction and then analyzed the relation between telomerase activity and other telomerase components such as human telomerase reverse transcriptase (TERT), human telomerase RNA component (hTR), human telomerase-associated protein (TEP1), telomeric repeat binding factor 1 (TRF1), TRF2- and TRF1-interacting, ankyrin-related ADP-ribose polymerase (tankyrase) as well as TRF1-interacting nuclear protein 2 (TIN2). Of twenty gastric carcinomas examined, 13 (65%), 14 (70%), 16 (80%), 12 (60%) and 13 (65%) expressed MRE11, RAD50, NBS1, Sir2 and hRap1 at higher levels than corresponding nonneoplastic gastric mucosa, respectively. No obvious correlation was observed between MRE11 complex expression and telomerase activity or expression of TERT, hTR, TEP1, tankyrase and TIN2. Carcinomas with high TRF1 expression expressed significantly higher levels of MRE11 and RAD50 than those with low TRF1 expression (p < 0.05). On the other hand, carcinomas with high TRF2 expression expressed significantly higher levels of MRE11, NBS1 and hRap1 than those with low TRF2 expression (p < 0.05). These results suggest that gastric carcinomas with high TRF1 and TRF2 expression may need a large quantity of the MRE11 complex. Moreover, gastric carcinomas with high TRF1 expression may require a large quantity of hRap1.
Matsutani
N
N
First Department of Pathology, Hiroshima University School of Medicine, Minami-ku, Hiroshima, Japan. norimaki@hiroshima-u.ac.jp
Yokozaki
H
H
Tahara
E
E
Tahara
H
H
Kuniyasu
H
H
Kitadai
Y
Y
Haruma
K
K
Chayama
K
K
Tahara
E
E
Yasui
W
W
D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C086930:RAD50 protein, S cerevisiae; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae