Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells

Abstract

Abstract.We recently reported the expression of an estradiollike molecule by a trematode parasite Schistosoma haematobium. We further established that this estradiol-like molecule is an antagonist of estradiol, repressing the transcriptional activity of the estrogen receptor (ER) in estrogen-responsive MCF7 cells and also that S. haematobium total antigen (Sh) contains estrogenic molecules detected by mass spectrometry. In the present study, we used HCV29 cells, a cell line derived from normal urothelial cells, as well as an in vivo model to evaluate the expression of ER in the bladders of Sh-instilled animals. We show that, similarly to MCF7 cells, Sh down-regulates the transcriptional activity of ER in HCV29 cells and also in the bladders of Sh-treated mice. The antiestrogenic activity of the S. haematobium extract and its repressive role in ER could have implications in the carcinogenic process in bladders with S. haematobium infection.

The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes

“…Moreover, new estrogenic molecules were identified in S. haematobium total antigen as well as in the serum of infected individuals with this parasitic disease that seem to be produced by this parasite [35]. ER transcriptional activity was suppressed in urothelial cells and ER expression was also suppressed in the bladders of mice in response to S. haematobium [36].…”

Targeting molecular signaling pathways of Schistosoma haemotobium infection in bladder cancer

“…The urothelium was always negative for ER protein expression in all animals of the four groups. 87 The controls of Group 2, sacrificed after 20 weeks, showed positive staining in the urethral epithelium and in the smooth muscle cells (SMC) in 80% (4 out of 5) of the bladders ( Table 1 and Fig. 3A-D).…”

“…Group 4, controls sacrificed after 40 weeks, showed positive ER expression in the urethral epithelium and in the smooth muscle cells (SMC) in 60% (3 out of 5) of the bladders. 87 This work addressed the regulation of expression of S. haematobium antiestrogenic activity as an important mechanism used by the parasite to influence ER transcription. The benefit that this ER repression may provide to the parasite could be explained by the following hypothesis: estradiol treatment as been shown to increase the smooth muscle density of the bladder in female rats.…”

“…Therefore HCV29 cells, a cell line of normal urothelial cells, and CD-1 mice were used to evaluate the expression of ER in the bladders of Sh-instilled animals. 87 Expression of ERa and ERb were analyzed in HCV29 cells after estradiol, electrophilic species. Some authors reported that these species are able to covalently bind DNA bases, forming stable adducts.…”

Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen–DNA adducts mediated pathway?

“…Cells were passaged every 5 days. Cells were serum-starved overnight before treatments (Botelho et al, 2012).…”