C. Bai et al., Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster, P NAS US, 97(3), 2000, pp. 1230-1235
Citations number
41
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Fas-mediated apoptosis is an important regulator of cell survival, and abno
rmalities in this system have been shown to result in a number of human pat
hological conditions. A secreted member of the tumor necrosis factor recept
or superfamily, DcR3, was recently reported to be amplified in human lung a
nd colon cancers as a negative regulator of Fas-mediated apoptosis. We iden
tified this gene, which we call M68. M68 genomic DNA, mRNA, and protein lev
els were examined in a series of human gastrointestinal tract tumors. Using
M68 immunohistochemistry and a scoring system similar to that used for HER
-2/neu, we found that M68 protein was overexpressed in 30 of 68 (44%) human
adenocarcinomas of the esophagus, stomach, colon, and rectum. Tumors exami
ned by Northern blot revealed M68 mRNA highly elevated in a similar fractio
n of primary tumors from the same gastrointestinal tract regions, as well a
s in the colon adenocarcinoma cell lines SW480 and SW1116. Further, we foun
d M68 protein to be overexpressed in a substantial number of tumors in whic
h gene amplification could not be detected by fluorescence in situ hybridiz
ation or quantitative genomic PCR, suggesting that overexpression of M68 ma
y precede amplification in tumors. Finally, we find that M68 lies within a
four-gene cluster that includes a novel helicase-like gene (NHL) related to
RAD3/ERCC2, a plasma membrane Ras-related GTPase and a member of the stath
min family, amplification or overexpression of which may also contribute to
cell growth and tumor progression.