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La Jolla Cancer Research Foundation, La Jolla, California 92037 [J. Y., J. N., Y. K., T. K-S.], and Department of Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya 320, Japan [J. A.]
A Mr 114,000 protein (p114) that specifically binds to nuclear matrix attachment DNA (matrix attachment region, MAR) from a breast carcinoma cell line SK-BR-3 was purified to near homogeneity. p114 strongly binds to a wild-type A+T-rich MAR probe with high unwinding propensity with a dissociation constant (Kd) of 10-9, while it exhibits substantially reduced binding to a mutated A+T-rich non-MAR probe, which lacks unwinding propensity. This binding specificity and affinity is similar 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 normal breast tissues, benign breast diseases, and immortalized epithelial MCF-10A cells. Thus, the MAR-binding activity of p114 is not merely reflecting cell proliferation, but it strongly associates with breast carcinomas. The p114 MAR-binding activity was found in all 43 human breast carcinoma specimens tested, without exception. Much stronger p114 MAR-binding activity was detected in poorly differentiated than well-differentiated carcinomas. p114 may be a reliable diagnostic and possibly prognostic marker for breast cancer.
1 This work was initially supported by the NIH Grants R01CA39681 (to T. K-S.) and R01 CA51377 (to Y. K.), and the latter part of this work was supported by Sankyo Co., Ltd. which provided equipment funds, and Grant 1RB-0381-LO1 from the Breast Cancer Research Program, University of California (to T. K-S.).
2 To whom requests for reprints should be addressed, at La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037. Fax: (619) 453-6217.
Received 10/24/95. Accepted 12/14/95.
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