IDENTIFICATION AND SIGNIFICANCE OF TUMOR MARKER MUC1/CA 15-3, IN METASTATIC BREAST CANCER

Abstract

Disease associated risk factors in premenopausal women includes professional and household stresses. While in post menopausal women the major factor is sedentary life style. Physiological characteristic have shown that the major risks associated with the aggressiveness of tumor are the receptor status especially triple negative (ER, PR and her2/neu) in both premenopausal and post menopausal women. Techniques of ELISA SEC, HPLC were tried to find out the method for estimation of the level of MUCI/CA15- 3 that showed an early detection and that was also economical. Computational protein modeling was used to predict secondary structure of MUC1. Predicted secondary structure of MUC1/CA 15-3 contains 6.0% helix, 7.9% strand or β-pleated sheet and 86.1% loop. Percentage composition shows an increased number of alanine, proline, serine, tyrosine, valine and glycine in helix, strand and turn or loop structure that indicates its basic and hydrophobic characteristics. MUC1/CA 15-3 comprises of an extracellular domain and a membrane associated domain. A junction of 3 amino acid units i.e. Cys-Gln-Cys between the extracellular subunit and transmembrane subunit is also observed. This motif is necessary for surface expression. The extracellular subunit consists of a tandem repeat unit that consist 20 amino acid residues i.e sapdnkpags and tappahgvts. This region of MUC1 may be used as vaccine for breast cancer. The subcellular subunit of MUC1 mainly consists of immunodominant DTR motif at 922 postion of the domain, is haeavily glycosylated and may protect the cell from any of the foreign body or tumor cell. The other subunit of MUC1/CA 15-3 consists of 17 amino acid residues. This subunit is associated with the plasma membrane. xixPost translational modifications (glycosylation, phosphorylation and myristoylation) are mainly observed in extracellular subunit. Several phosphorylation sites, Myristoylation sites and some glycosylation sites of tandem repeat region were predicted in MUC1/CA 15-3. It was observed that due to these modifications, the protein performed different functions. Alignment of the sequence of MUC1/CA 15-3 with the other family member of mucins (MUC2- MUC12) shows highest homology of MUC1/CA 15-3 with MUC4. The property of breast tumor to produce mucinous antigen was used for the synthesis of vaccine using the experimental mice. Electrophoretic technique was used to confirm the production of antibody that may be effective against antigen of MUC1/CA 15-3. The conclusion is that CA 15-3 is a transmembrane glycoprotein having basic and hydrophobic charecterstics. The most important part of this protein is extracellular and transmembrane subunits. These subunits of protein undergo posttranslational modification and are important in immunization and vaccine formation.