A MATRIX ATTACHMENT REGION (MAR)-BINDING ACTIVITY DUE TO A P114 KILODALTON PROTEIN IS FOUND ONLY IN HUMAN BREAST CARCINOMAS AND NOT IN NORMAL AND BENIGN BREAST DISEASE TISSUES

A M(r) 114,000 protein (p114) that specifically binds to nuclear matri x attachment DNA (matrix attachment region, MAR) from a breast carcino ma cell line SK-BR-3 was purified to near homogeneity, p114 strongly b inds to a wild-type A+T-rich MAR probe with high unwinding propensity with a dissociation constant (K-d) of 10(-9), while it exhibits substa ntially reduced binding to a mutated A+T-rich non-MAR probe, which lac ks unwinding propensity. This binding specificity and affinity is simi lar to the previously cloned thymocyte-associated MAR-binding protein SATB1. By Southwestern blot analysis, the MAR-binding activity of p114 is detectable in human breast carcinomas but is undetectable in norma l breast tissues, benign breast diseases, and immortalized epithelial MCF-10A cells, Thus, the MAR-binding activity of p114 is not merely re flecting cell proliferation, but it strongly associates with breast ca rcinomas, The p114 MAR-binding activity was found in all 43 human brea st carcinoma specimens tested, without exception, Much stronger p114 M AR-binding activity was detected in poorly differentiated than well-di fferentiated carcinomas, p114 may be a reliable diagnostic and possibl y prognostic marker for breast cancer.