Isolation and characterization of a pepsin C zymogen produced by human breast tissues.
An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies.
D000595:Amino Acid Sequence; D001940:Breast / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D002402:Cathepsin D / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004792:Enzyme Precursors / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005348:Fibrocystic Breast Disease / Q000201:enzymology* / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000032:analysis* / Q000235:genetics; D010435:Pepsinogens / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D004792:Enzyme Precursors; D010435:Pepsinogens; D012313:RNA; D004247:DNA; D010434:Pepsin A; C020557:gastricsin; D002402:Cathepsin D