Thus the genetically determined variation at the PUM locus accounts for much of the electrophoretic heterogeneity of the mucin-type glycoproteins present in breast cancer and serum from breast cancer patients that has been reported previously.
From the comparative analysis presented here it is concluded that the gene coding for H23 antigen furnishes a most useful marker for human breast cancer.
Tumour and blood leukocyte DNAs from sporadic breast cancer patients were examined for chromosome 1 loss of heterozygosity using a probe for a polymorphic epithelial mucin, PEM, which is expressed in greater than 92% of breast carcinomas as well as in normal lactating breast tissue.
Compared with corresponding normal tissue, MUC1 mRNA levels were increased in breast cancer and well-differentiated lung cancers, and MUC3 mRNA was increased in gastric adenocarcinomas.
Specific mucin gene expression was determined using cDNA probes for 2 distinct intestinal mucins (MUC-2 and MUC-3) and one breast cancer mucin (MUC-1).
MUC1 mRNA expression was detected by RT-PCR in MCF-7 cells and in all 15 primary breast carcinomas but not in control lymph nodes taken from patients with benign diseases.
Although it is known that human breast cancer tissue expresses at least 2 MUC1 type 1 membrane proteins (a polymorphic high molecular weight MUC1 glycoprotein that contains a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein that is not polymorphic and is lacking this repeat array) their function in the development of human breast cancer has remained elusive.
To find means of making this recognition event into a potent immune response to breast cancer, we used a murine tumor model and have examined the parameters of the immune response to human mucin (MUC1) expressed in murine BALB/c 3T3 cells.
We describe here the construction of recombinant vaccinia viruses co-expressing a tumour associated antigen (MUC 1) and an "adjuvant" cytokine, which have potential applications in the active immunotherapy of breast cancer.
Murine mAb 115D8 directed against episialin (MUC1/MAM6, epithelial membrane Ag) was used in combination with goat anti-mouse-coated magnetic microbeads to purify human T47D breast carcinoma cells (115D8+, MDR1-) from different mixtures with COLO320 human colon carcinoma cells (115D8-, MDR1+) and to purify carcinoma cells from FNA taken from axillary lymph node metastases in breast cancer patients.
These results demonstrate the usefulness of both MUC1 RT-PCR and keratin 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes, and also indicate the superiority of keratin 19 RT-PCR over MUC1 RT-PCR because of its higher detection sensitivity.
These results identify a genetic mechanism responsible for MUC1 gene overexpression and support the hypothesis that a gene dosage effect of the long arm of chromosome 1 may be involved in the pathogenesis of breast cancer.
Using the expression of pS2 (a trefoil peptide expressed in breast cancer cells), MUC1 (a member of the mucin family) and ER (the human estrogen receptor) genes as estrogen-responsive reporter genes, the effects of estradiol and NP on human breast cancer cells-MCF-7 were studied.
Amplification of this region had not previously been associated with sarcoma development, but occasional amplification of CACY/S100A6 and MUC1 in 1q21 had been reported for melanoma and breast carcinoma respectively.