Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues.
Hereditary nonpolyposis colorectal cancer is caused by inherited mutations of mismatch repair genes. We developed monoclonal antibodies to the prototype human mismatch repair gene hMSH2 and used them to detect an immunoreactive protein of M(r) 100,000 in mismatch-proficient cell lines. In addition, a M(r) 150,000 protein coimmunoprecipitated with the hMSH2 gene product in cell lines expressing hMSH2. Immunohistochemistry demonstrated that the hMSH2 protein was exclusively nuclear. Whereas the hMSH2 protein was expressed in a variety of tissues, the most striking pattern was observed in esophageal and intestinal epithelia, where expression was limited to the replicating compartment. Neoplastic cells within benign and malignant mismatch repair-proficient tumors expressed the protein, but no hMSH2 immunoreactivity was observed in the colorectal tumors of patients with germline hMSH2 mutation. These results have implications for tumorigenic mechanisms and, potentially, for diagnosis.
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
F S
FS
Leach
K
K
Polyak
M
M
Burrell
K A
KA
Johnson
D
D
Hill
M G
MG
Dunlop
A H
AH
Wyllie
P
P
Peltomaki
A
A
de la Chapelle
S R
SR
Hamilton
K W
KW
Kinzler
B
B
Vogelstein
D000818:Animals; D000911:Antibodies, Monoclonal; D003106:Colon / Q000737:chemistry; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D004947:Esophagus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051718:MutS Homolog 2 Protein; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein