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ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage

Overview of attention for article published in Endocrinology, November 2017
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Title
ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage
Published in
Endocrinology, November 2017
DOI 10.1210/en.2017-00652
Pubmed ID
Authors

Ödül Karayazi Atici, Anna Urbanska, Sesha Gopal Gopinathan, Florence Boutillon, Vincent Goffin, Carrie S Shemanko

Abstract

Prolactin acts as a survival factor for breast cancer cells, but the prolactin signaling pathway and the mechanism is unknown. Previously, we identified the master chaperone, heat shock protein 90α (HSP90α), as a prolactin-Janus-Kinase-(JAK2)-signal-transducer-and-activator-of-transcription-5-(STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of prolactin-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase protein (ATM) plays a critical role in the cellular response to double strand DNA damage. Prolactin increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the prolactin receptor, as the prolactin receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxy geldanamycin and BIIB021, reduced the prolactin-mediated increase in cell viability of doxorubicin treated cells, and led to a decrease in JAK2, ATM and phospho-ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the prolactin-mediated increase in cell viability of DNA damaged cells, supporting the involvement of each, as well as the cross-talk of ATM with the prolactin pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor, KU55933, and doxorubicin, and also between the HSP90 inhibitor, BIIB021, and doxorubicin. Short interfering RNA, directed against ATM, prevented the PRL-mediated increase in cell survival in both 2D and 3D collagen gel cultures, and in clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the prolactin-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA damaging agents.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 31%
Student > Bachelor 2 13%
Student > Doctoral Student 1 6%
Other 1 6%
Lecturer 1 6%
Other 1 6%
Unknown 5 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 56%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Unknown 6 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 September 2021.
All research outputs
#15,398,481
of 25,839,971 outputs
Outputs from Endocrinology
#1,748
of 1,779 outputs
Outputs of similar age
#232,429
of 449,154 outputs
Outputs of similar age from Endocrinology
#1
of 1 outputs
Altmetric has tracked 25,839,971 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,779 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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