MUC4 is a membrane-bound mucin and is considered as the human homologue of
the rat sialomucin complex (SMC). The deduced structural organization of th
e wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large ami
no mucin type subunit (MUC4 alpha) and a transmembrane subunit (MUC4 beta).
MUC4 beta is a membrane-bound growth factor like subunit and contains thre
e EGF-like domains. The MUC4 gene is expressed in several normal tissues li
ke trachea, lung, and testis. It is not expressed in a normal human pancrea
s; however, its dysregulation results in high levels of expression in pancr
eatic tumors and tumor cell lines. Recently, we have demonstrated the prese
nce of alternative splice events in the 3'-end of the MUC4 cDNA that genera
ted new putative variants (sv1-sv10) in normal human testis and in a pancre
atic tumor cell line (HPAF). In search of MUC4 variant(s) that are specific
to pancreatic adenocarcinoma, we investigated the splicing phenomena in th
e MUC4 cDNA sequence by using a large panel of pancreatic tumor cell lines.
We have identified ten alternative splice events located downstream to the
central large tandem repeat domain. These splice events generated 12 varia
nt species (sv4, sv9, sv10-18, and sv21) of MUC4 cDNAs. The deduced amino a
cid sequence of these variant MUC4 cDNAs revealed two distinct types: a fam
ily of secreted and a membrane-associated variant form. Among the members o
f MUC4 secreted variant family, three (sv4, sv12, and sv13) of ten showed a
short 144 residue COOH-terminus compared to 1154 residues in WT-MUC4. The
variants with this short COOH-terminus (144 residues) was found in 37% (4/1
1) of the tumor lines. The putative membrane-bound variant sv10 was detecte
d in 37% (4/11) pancreatic tumor cell lines but not in any normal human tis
sues. In conclusion, we have identified novel splice variant(s) of MUC4 in
pancreatic adenocarcinoma. Teratogenesis Carcinog. Mutagen. 21:83-96, 2001.
(C) 2001 Wiley-Liss, Inc.