Regulation of Membrane Protease Associated with Breast Cancer.
Annual rept. 1 Aug 95-31 Jul 96,
GEORGETOWN UNIV WASHINGTON DC
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We initially proposed to determine the role of mp 170 seprase in the metastasis of breast cancer. The mp170 seprase exhibits its highest identity 94 with the integral membrane protein Fibroblast Activation Protein Alpha FAPthat is expressed in vivo in carcinomas and sarcomas but whose function is unknown. The in vitro breast carcinoma line MDA-MB-436 which is known to express mp170 seprase would appear to be a good candidate for transfection experiments with sense and antisense cDNA constructs of mp170 seprase. Using the in vitro extracellular matrix ECM invasiondegradation assay we could monitor the effects of the overexpression and underexpression of this gelatinase on the invasive phenotype of MDA-MB-436 as well as other cell lines MDA-MB-231 etc. at various stages of neoplastic development. The deduced amino acid sequence predicts a type II integral membrane protein of 760 amino acids. And its carboxyl terminus contains a putative catalytic region which is homologous to the nonclassical serine protease subfamily represented by the ectopeptidase Dipeptidyl Peptidase IV DPPIV. Therefore, our first priority is to isolate a cDNA clone that encodes the entire open reading frameORF of mp170 seprase.
- Anatomy and Physiology
- Medicine and Medical Research
- Organic Chemistry