Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas.
BACKGROUND
Mucins are considered important markers for early diagnosis and targeted therapy due to their aberrant and unique expression pattern during malignant progression of carcinomas. Recent findings have provided substantial evidence for the involvement of transmembrane mucins, MUC1 and MUC4, in altered cell signaling, tumor growth, and metastasis.


METHODS
Immunohistochemical analyses were performed on prostate tumor tissues for expression profiling of the two transmembrane mucins, MUC1 and MUC4. In cancer cell lines, the expression was studied by RT-PCR and immunoblot analyses. Cells were treated with DNA-methylase and histone-deacetylase inhibitors to examine the implication of epigenetic mechanism(s) in MUC4 regulation.


RESULTS
The expression of MUC4 was significantly down regulated in prostate cancer tissues (n=38, P=0.0026) compared to normal/benign prostatic hyperplastic regions. A faint to moderate staining was observed in 26.3% cases of cancer, while 84.2% cases of adjacent normal were positive for MUC4 with moderate to strong staining in most cases. Similar observations were made in immortalized normal prostate epithelial and cancer cell lines. MUC1 also showed a reduced expression in prostate tumor tissues; however, its expression was comparable in all normal prostate epithelial and cancer cell lines. Interestingly, we also found that epigenetic mechanism(s) might be implicated in MUC4 gene silencing.


CONCLUSIONS
Our data suggest that MUC4 downregulation may be of significance for diagnostic applications in prostate cancer.
Singh
Ajay P
AP
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
Chauhan
Subhash C
SC
Bafna
Sangeeta
S
Johansson
Sonny L
SL
Smith
Lynette M
LM
Moniaux
Nicolas
N
Lin
Ming-Fong
MF
Batra
Surinder K
SK
D000941:Antigens / Q000096:biosynthesis*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C060192:MUC1 protein, human; C524658:MUC4 protein, human; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins