Inhibition of Microbial Beta-Glucuronidase Does Not Prevent Breast Carcinogenesis in the Polyoma Middle T Mouse

Purpose To demonstrate whether inhibition of intestinal microbial beta (β)-glucuronidase (BGUS) abrogates tumor formation in a MMTV-PyMT mouse breast cancer model. Methods Female MMTV-PyMT heterozygote mice (4 weeks old) were randomized to oral gavage with vehicle or UNC10201652 (20 μg/day), a microbial BGUS inhibitor, for 9 weeks. The entire animal carcass was assessed for tumor deposits by histology and immunohistochemical staining for tumor (Ki67, PCNA) and breast specific (ER, PR, Cyclin D1, aSMA, Integrin β1) markers. Results The MMTV-PyMT breast pathology in our study simulates prior published reports of tumor incidence and aggressiveness. There was no significant difference in the tumor histology, number of tumors (lesions), and patterns of spread of tumors in the UNC10201652 versus the vehicle treated mice. Similarly, there were no significant differences in the semi-quantitative scores for expression of ER, PR, Ki67, PCNA, or Integrin β1. There were also no major differences seen in qualitative screening of Cyclin D1 and aSMA. Conclusions MMTV-PyMT mice administered UNC10201652, when compared to vehicle treated mice, show a similar abundance of breast tumor (and tumor initiating) lesions ranging from hyperplasia to frank carcinoma. There is a trend, however small, that the incidence of hyperplastic and adenomas may be decreased in UNC10201652 treated mice. Further refined dosing strategies in MMTV-PyMT are planned to clarify its biological significance. To our knowledge this is the first report of use of any BGUS inhibitor in chemoprevention of breast tumors using a genetic model simulating human breast cancer.