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.