Mutational analysis of proapoptotic integrin beta 3 cytoplasmic domain in common human cancers.
OBJECTIVE
Mounting evidence indicates that deregulation of apoptosis is involved in the mechanisms of cancer development. Integrins are cell adhesion receptors that mediate cell survival and migration. A recent study showed that unligated integrin beta 3 (ITGB3) induced apoptosis by recruitment of caspase-8. The aim of the present study was to explore the possibility that genetic alteration of the ITGB3 gene is involved in the development of human cancers possibly by inactivating the apoptosis function of ITGB3.


METHODS
We analyzed the coding region of the cytoplasmic domain of the human ITGB3 gene for the detection of somatic mutations in 100 gastric, 90 colorectal, 100 non-small cell lung, 43 urinary bladder and 50 head-neck cancers by a polymerase chain reaction-based, single-strand conformation polymorphism.


RESULTS
We found an identical ITGB3 mutation in two unrelated patient samples (one in colorectal and the other in bladder cancer). The ITGB3 mutation was a missense mutation which would substitute an amino acid (E757K).


CONCLUSIONS
The data suggested that the proapoptotic ITGB3 cytoplasmic domain is rarely mutated in common human cancers and may not play an important role in the development of the cancers.
Yoo
Nam Jin
NJ
Department of Pathology, College of Medicine, Catholic University of Korea, Seoul, Korea.
Soung
Young Hwa
YH
Lee
Sung Hak
SH
Jeong
Eun Goo
EG
Lee
Sug Hyung
SH
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D007822:Laryngeal Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D012494:Sampling Studies; D013274:Stomach Neoplasms / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; D039661:Integrin beta3; D009363:Neoplasm Proteins