Abstract P6-03-09: Role of IL-6 in promoting endocrine therapy and palbociclib resistance estrogen receptor positive breast cancer cells

2020 ◽  
Author(s):  
Nicole M Kettner ◽  
Tuyen Bui ◽  
Xian Chen ◽  
Kelly K Hunt ◽  
Debu Tripathy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Endocrine Therapy ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals Understanding the Role of Estrogen Receptor Status in PRODH/POX-Dependent Apoptosis/Survival in Breast Cancer Cells

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1314
Author(s):  
Sylwia Lewoniewska ◽  
Ilona Oscilowska ◽  
Antonella Forlino ◽  
Jerzy Palka
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Collagen Biosynthesis ◽  
Estrogen Receptor Positive ◽  
Er Status ◽  
Positive Breast Cancer

It has been suggested that activation of estrogen receptor α (ER α) stimulates cell proliferation. In contrast, estrogen receptor β (ER β) has anti-proliferative and pro-apoptotic activity. Although the role of estrogens in estrogen receptor-positive breast cancer progression has been well established, the mechanism of their effect on apoptosis is not fully understood. It has been considered that ER status of breast cancer cells and estrogen availability might determine proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis. PRODH/POX is a mitochondrial enzyme that converts proline into pyrroline-5-carboxylate (P5C). During this process, ATP (adenosine triphosphate) or ROS (reactive oxygen species) are produced, facilitating cell survival or death, respectively. However, the critical factor in driving PRODH/POX-dependent functions is proline availability. The amount of this amino acid is regulated at the level of prolidase (proline releasing enzyme), collagen biosynthesis (proline utilizing process), and glutamine, glutamate, α-ketoglutarate, and ornithine metabolism. Estrogens were found to upregulate prolidase activity and collagen biosynthesis. It seems that in estrogen receptor-positive breast cancer cells, prolidase supports proline for collagen biosynthesis, limiting its availability for PRODH/POX-dependent apoptosis. Moreover, lack of free proline (known to upregulate the transcriptional activity of hypoxia-inducible factor 1, HIF-1) contributes to downregulation of HIF-1-dependent pro-survival activity. The complex regulatory mechanism also involves PRODH/POX expression and activity. It is induced transcriptionally by p53 and post-transcriptionally by AMPK (AMP-activated protein kinase), which is regulated by ERs. The review also discusses the role of interconversion of proline/glutamate/ornithine in supporting proline to PRODH/POX-dependent functions. The data suggest that PRODH/POX-induced apoptosis is dependent on ER status in breast cancer cells.

scholarly journals Endocrine Therapy of Estrogen Receptor-Positive Breast Cancer Cells: Early Differential Effects on Stem Cell Markers

2017 ◽  
Vol 7 ◽  
Author(s):  
Euphemia Y. Leung ◽  
Marjan E. Askarian-Amiri ◽  
Debina Sarkar ◽  
Carole Ferraro-Peyret ◽  
Wayne R. Joseph ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Stem Cell ◽  
Cancer Cells ◽  
Endocrine Therapy ◽  
Breast Cancer Cells ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Role of AIB1 for Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Cells

Oncology ◽  
2008 ◽  
Vol 75 (3-4) ◽  
pp. 159-168 ◽  
Author(s):  
Qingbo Su ◽  
Sanyuan Hu ◽  
Haidong Gao ◽  
Rong Ma ◽  
Qifeng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals Palbociclib and fulvestrant act in synergy to modulate central carbon metabolism in breast cancer cells

2018 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V Lee ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Pentose Phosphate Pathway ◽  
Metabolic Pathways ◽  
Breast Cancer Cells ◽  
Pentose Phosphate ◽  
List Type ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.

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