PMID- 10463611
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 16
DP  - 1999 Aug 15
TI  - Two novel mucin genes down-regulated in colorectal cancer identified by
      differential display.
PG  - 4083-9
AB  - Epithelial mucins are large, secreted and cell surface glycoproteins involved in 
      epithelial cell protection, adhesion modulation, and signaling. Using
      differential display, we have identified two novel mucin cDNAs (dd34 and dd29),
      hereafter designated MUC11 and MUC12, respectively, that are down-regulated in
      colorectal cancers. Northern blots demonstrated polydisperse signals
      characteristic of mucin transcripts in RNA from normal colon that were absent in 
      colorectal cancer. Both cDNAs were mapped by fluorescence in situ hybridization
      to chromosome band 7q22, the location of the MUC3 mucin gene, thus suggesting
      that there may be a cluster of mucin genes at this locus. The sequences of both
      differential display clones were extended by a combination of screening libraries
      and PCR. The 2.8-kb MUC11 cDNA composite encoded 35 serine/threonine-rich,
      mucin-like degenerate 28 amino acid tandem repeats. The MUC12 cDNA composite
      encoded a putative transmembrane mucin containing two extracellular
      cysteine-rich, EGF-like domains, a coiled-coil region, and a mucin-like domain
      consisting of 28 amino acid degenerate tandem repeats. Distinct patterns of
      expression of MUC11, MUC12, and MUC3 mRNAs were observed in a range of normal
      human tissues. MUC12 mRNA was not expressed in any of six colorectal cancer cell 
      lines examined and was down-regulated or absent in 6 of 15 (40%) tumors compared 
      with matched normal colonic tissue. In contrast, MUC11 showed a different pattern
      of mRNA expression, with four of these lines showing low levels and the other two
      lines showing relatively high levels of MUC11 transcripts. Expression of MUC11
      was down-regulated in the tumors of 12 of 15 (80%) paired samples. Structural
      homology of MUC12 with rat, mouse, and human MUC3 and human and rat MUC4/ASGP2
      indicate that there is a distinct subfamily of transmembrane mucins with
      conserved epidermal growth factor domains. The homology of MUC12 with epidermal
      growth factor-like growth factors and its down-regulation in colorectal cancers, 
      together with known interactions between rat MUC4 and c-erbB-2 growth factor
      receptors, suggests that MUC12 may be involved in epithelial cell growth
      regulation.
FAU - Williams, S J
AU  - Williams SJ
AD  - Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston,
      Australia.
FAU - McGuckin, M A
AU  - McGuckin MA
FAU - Gotley, D C
AU  - Gotley DC
FAU - Eyre, H J
AU  - Eyre HJ
FAU - Sutherland, G R
AU  - Sutherland GR
FAU - Antalis, T M
AU  - Antalis TM
LA  - eng
SI  - GENBANK/AF147790
SI  - GENBANK/AF147791
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Mucins)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Colorectal Neoplasms/*genetics
MH  - Down-Regulation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mucins/biosynthesis/*genetics
MH  - Neoplasm Proteins/biosynthesis/genetics
MH  - Rats
MH  - Sequence Alignment
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Aug 15;59(16):4083-9.