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

Abstract

Purpose: To demonstrate whether inhibition of intestinal microbial beta (b)-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 b1) 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 b1. 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.

Investigating the Metabolism of Estrogens in Ligilactobacillus salivarius Strains Isolated from Human Milk and Vaginal Microbiota

“…Recently, Ervin et al [ 44 ] have demonstrated that the administration of fecal samples rich in these enzymatic activities to mice did not correlate with an increase in tumorogenesis, suggesting that the function of these enzymes could be a way of reactivating estrogens that can be further metabolized in different ways (e.g., hydrolyzed, epimerized, oxidized, methylated) in distal sites. In parallel, Beck et al [ 75 ] demonstrated that treatment with β-glucuronidase inhibitors did not prevent breast cancer in mice.…”