|
 Curently online :
8 |
|
 Total visitors :
7475639 |
|
|
Progesterone activation of zebrafish mineralocorticoid receptor may influence growth of some transplanted tumors
Sunday, 2018/04/01 | 06:13:18
|
|
Yoshinao Katsu and Michael E. Baker PNAS March 27, 2018. 115 (13) E2908-E2909
Fior et al. (1, 2) provide strong evidence for the benefits of studying the effects of drugs on the growth of human colon cancer explants in zebrafish to identify those drugs that will be effective in treating a specific patient’s tumor. Moreover, their work suggests that a similar approach using xeno-transplants of other diseased tissues in zebrafish may be used profitably to find personalized drugs to treat these diseases. There is, however, a concern in using this method for personalized treatment of endocrine-dependent cancers, such as estrogen-dependent breast tumors, in which the progesterone receptor (PR) is important because of its interaction with estrogen receptor signaling. Recently, the zebrafish mineralocorticoid receptor (MR) has been found to be activated by progesterone (Fig. 1), which is in contrast to human MR, for which progesterone is an antagonist. Thus, progesterone signaling in tumor transplants in zebrafish affects transcriptional activation of the MR as well as the PR, potentially confounding the results for human physiology. Mifepristone (RU486), an antagonist for human PR, does not inhibit either aldosterone or progesterone activation of zebrafish MR (Fig. 1), in accord with Sturm et al.’s (2005) finding for trout MR. Thus, RU486 may be used to selectively inactivate zebrafish PR, although progesterone activation of the MR would remain a problem.
See: http://www.pnas.org/content/115/13/E2908
Figure 1: RU486 does not inhibit activation of zebrafish MR by either progesterone (Prog) or aldosterone (Aldo). Zebrafish MR was expressed in HEK293 cells with a mouse mammary tumor virus (MMTV)-luciferase reporter. Cells were treated with either 0.5 nM Aldo alone or with 10 nM or 100 nM RU486, or with 1 nM progesterone alone or with 10 nM or 100 nM RU486 or with vehicle alone (DMSO). Results are expressed as means ± SEM, n = 3. The y axis indicates fold-activation compared with the control vector with DMSO alone as 1. |
Back
Print
View: 363
|
|
[ Other News ]___________________________________________________
|
(14).png "Progesterone activation of zebrafish mineralocorticoid receptor may influence growth of some transplanted tumors")
