Publication
Prostate cancer is very frequent and is, in many countries, the third-leading cause of cancer related death in men. While early diagnosis and treatment by surgical removal is often curative, metastasizing prostate cancer has a very bad prognosis. Based on the androgen-dependence of prostate epithelial cells, the standard treatment is blockade of the androgen receptor (AR). However, nearly all patients suffer from a tumor relapse as the metastasizing cells become AR-independent.
In our study we show a counter-regulatory link between AR and NF-κB both in human cells and in mouse models of prostate cancer, implying that inhibition of AR signaling results in induction of NF-κB-dependent inflammatory pathways, which may even foster the survival of metastasizing cells.
This could be shown by reporter gene assays, DNA-binding measurements, and immune-fluorescence microscopy, and furthermore by a whole set of computational methods using a variety of datasets. Interestingly, loss of PTEN, a frequent genetic alteration in prostate cancer, also causes an upregulation of NF-κB and inflammatory activity.
Finally, we present a mathematical model of a dynamic network between AR, NF-κB/IκB, PI3K/PTEN, and the oncogene c-Myc, which indicates that AR blockade may upregulate c-Myc together with NF-κB, and that combined anti-AR/anti-NF-κB and anti-PI3K treatment might be beneficial.
J. Basílio, B. Hochreiter, B. Hoesel, E. Sheshori, M. Mussbacher, R. Hanel, J. A. Schmid, Antagonistic Functions of Androgen Receptor and NF-κB in Prostate Cancer—Experimental and Computational Analyses, Cancers 14(4) (2022) 6164.
Signup
Cookie | Duration | Description |
---|---|---|
cookielawinfo-checkbox-analytics | 1 year | Set by the GDPR Cookie Consent plugin, this cookie records the user consent for the cookies in the "Analytics" category. |
cookielawinfo-checkbox-functional | 1 year | The GDPR Cookie Consent plugin sets the cookie to record the user consent for the cookies in the category "Functional". |
cookielawinfo-checkbox-necessary | 1 year | Set by the GDPR Cookie Consent plugin, this cookie records the user consent for the cookies in the "Necessary" category. |
CookieLawInfoConsent | 1 year | CookieYes sets this cookie to record the default button state of the corresponding category and the status of CCPA. It works only in coordination with the primary cookie. |
PHPSESSID | session | This cookie is native to PHP applications. The cookie stores and identifies a user's unique session ID to manage user sessions on the website. The cookie is a session cookie and will be deleted when all the browser windows are closed. |
viewed_cookie_policy | 1 year | The GDPR Cookie Consent plugin sets the cookie to store whether or not the user has consented to use cookies. It does not store any personal data. |
Cookie | Duration | Description |
---|---|---|
mec_cart | 1 month | Provides functionality for our ticket shop |
VISITOR_INFO1_LIVE | 6 months | YouTube sets this cookie to measure bandwidth, determining whether the user gets the new or old player interface. |
VISITOR_PRIVACY_METADATA | 6 months | YouTube sets this cookie to store the user's cookie consent state for the current domain. |
YSC | session | Youtube sets this cookie to track the views of embedded videos on Youtube pages. |
yt-remote-connected-devices | never | YouTube sets this cookie to store the user's video preferences using embedded YouTube videos. |
yt-remote-device-id | never | YouTube sets this cookie to store the user's video preferences using embedded YouTube videos. |
yt.innertube::nextId | never | YouTube sets this cookie to register a unique ID to store data on what videos from YouTube the user has seen. |
yt.innertube::requests | never | YouTube sets this cookie to register a unique ID to store data on what videos from YouTube the user has seen. |
Cookie | Duration | Description |
---|---|---|
_ga | 1 year | Google Analytics sets this cookie to calculate visitor, session and campaign data and track site usage for the site's analytics report. The cookie stores information anonymously and assigns a randomly generated number to recognise unique visitors. |
_ga_* | 1 year | Google Analytics sets this cookie to store and count page views. |
_gat_gtag_UA_* | 1 min | Google Analytics sets this cookie to store a unique user ID. |
_gid | 1 day | Google Analytics sets this cookie to store information on how visitors use a website while also creating an analytics report of the website's performance. Some of the collected data includes the number of visitors, their source, and the pages they visit anonymously. |