Androgens & a self-sustained quiescent state.

[pjoshea13]

New French study, below.

"Transient exposure to androgens induces a remarkable self-sustained quiescent state in dispersed prostate cancer cells."

"Overall, our data suggest that self-sustained but fully reversible quiescent states might constitute a general response of dispersed cancer cells to stress conditions."

"In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells."

Not sure what that means, but could it explain how PCa cells can remain dormant for many years?

-Patrick

ncbi.nlm.nih.gov/pubmed/284...

Cell Cycle. 2017 Apr 20:1-15. doi: 10.1080/15384101.2017.1310345. [Epub ahead of print]

Transient exposure to androgens induces a remarkable self-sustained quiescent state in dispersed prostate cancer cells.

Bui AT1, Huang ME2, Havard M1, Laurent-Tchenio F1, Dautry F1, Tchenio T1.

Author information

1

a LBPA, UMR8113 ENS Cachan - CNRS, Ecole Normale Supérieure de Cachan , Cachan, Cedex , France.

2

b Institut Curie, PSL Research University, CNRS UMR3348, Université Paris-Saclay , Orsay , France.

Abstract

Cellular quiescence is a reversible cell growth arrest that is often assumed to require a persistence of non-permissive external growth conditions for its maintenance. In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon required the set-up of a sustained redox imbalance and TGFβ/BMP signaling that were dependent on culturing cells at low density. At medium cell density, androgens failed to induce such a self-sustained quiescent state, which correlated with a lesser induction of cell redox imbalance and oxidative stress markers like CDKN1A. These effects of androgens could be mimicked by transient overexpression of CDKN1A that triggered its own expression and a sustained SMAD phosphorylation in cells cultured at low cell density. Overall, our data suggest that self-sustained but fully reversible quiescent states might constitute a general response of dispersed cancer cells to stress conditions.

KEYWORDS:

Androgen; BMP; CDKN1A; cellular quiescence; feedback loops; oxidative stress; prostate cancer

PMID: 28426320 DOI: 10.1080/15384101.2017.1310345

[Neal-Snyder]

Hi Patrick,

If we stop that critical sentence before the "hit & run," is it saying that androgen treatment could cause a period of remission? Thanks.

Neal

[pjoshea13]

Neal,

Yes - but for dispersed cells.

-Patrick

[AlanMeyer]

I thought I'd look at the full text to learn more about this. It turns out that you can look at the article for up to 24 hours for $50. However for the low rate of just $154 you can read the whole issue of the journal for 30 days. What a bargain! But I decided to pass and wait for it to go on sale.

Alan

[Hidden in reply to AlanMeyer]

fifty free download are available at researchgate.net/publicatio.... Please download only one. I could answer to some questions but have not much time.

Thierry

[Hidden]

Hello,

The role of this kind of dormancy may be indeed very important in the control of metastases growth at its initial step. Slight oxidative stresses that promote dormancy could be naturally triggered by natural nutriments, physiologic or supra-physiologic levels of androgens. Recent finding that will be fully verified in one or two years showed that in some conditions dormancy could be induced in high density prostate cancer cells.

Thierry

[Hidden]

fifty free download of the complete data are available at researchgate.net/publicatio... Please download only one. I could answer to some questions but have not much time.

Thierry