Ja. Uria et al., STRUCTURE AND EXPRESSION IN BREAST-TUMORS OF HUMAN TIMP-3, A NEW MEMBER OF THE METALLOPROTEINASE INHIBITOR FAMILY, Cancer research, 54(8), 1994, pp. 2091-2094
A new member of the metalloproteinase inhibitor family of proteins has
been cloned from a complementary DNA library derived from a human bre
ast tumor. The isolated complementary DNA contains an open reading fra
me 633 base pairs long, encoding a polypeptide of 211 amino acids, whi
ch has been called tissue inhibitor of metalloproteinase 3 (TIMP-3). T
his protein displays low sequence similarity to the previously known h
uman TIMPs but shows a high degree of similarity with chicken inhibito
r of metalloproteinase 3, a recently described metalloproteinase inhib
itor stimulated during oncogenic transformation of chicken fibroblasts
and with the ability to promote some phenotypic properties of transfo
rmed cells. Northern blot analysis of RNA from human tissues revealed
that the TIMP-3 gene is expressed in placenta and uterus but not in li
ver and ovary. In addition, TIMP-3 transcripts were detected in all br
east carcinomas examined. On the basis of these expression data in bre
ast tumors, together with its high degree of structural homology with
chicken inhibitor of metalloproteinase 3, a possible role for human TI
MP-3 in the regulation of connective tissue turnover and remodeling is
proposed.