EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs



RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs



Plos One 8(11): E78641-E78641



Triple negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which only chemotherapy and radiation therapy are currently available. The retinoblastoma (RB1) tumor suppressor is frequently lost in human TNBC. Knockdown of RB1 in luminal BC cells was shown to affect response to endocrine, radiation and several antineoplastic drugs. However, the effect of RB1 status on radiation and chemo-sensitivity in TNBC cells and whether RB1 status affects response to divergent or specific treatment are unknown. Using multiple basal-like and claudin-low cell lines, we hereby demonstrate that RB-negative TNBC cell lines are highly sensitive to gamma-irradiation, and moderately more sensitive to doxorubicin and methotrexate compared to RB-positive TNBC cell lines. In contrast, RB1 status did not affect sensitivity of TNBC cells to multiple other drugs including cisplatin (CDDP), 5-fluorouracil, idarubicin, epirubicin, PRIMA-1(met), fludarabine and PD-0332991, some of which are used to treat TNBC patients. Moreover, a non-biased screen of ∼3400 compounds, including FDA-approved drugs, revealed similar sensitivity of RB-proficient and -deficient TNBC cells. Finally, ESA(+)/CD24(-/low)/CD44(+) cancer stem cells from RB-negative TNBC lines were consistently more sensitive to gamma-irradiation than RB-positive lines, whereas the effect of chemotherapy on the cancer stem cell fraction varied irrespective of RB1 expression. Our results suggest that patients carrying RB-deficient TNBCs would benefit from gamma-irradiation as well as doxorubicin and methotrexate therapy, but not necessarily from many other anti-neoplastic drugs.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333564

Download citation: RISBibTeXText

PMID: 24265703

DOI: 10.1371/journal.pone.0078641



Related references

Protein expression of DNA damage repair proteins dictates response to topoisomerase and PARP inhibitors in triple-negative breast cancer. Plos One 10(3): E0119614-E0119614, 2016

Bevacizumab Addition in Neoadjuvant Treatment Increases the Pathological Complete Response Rates in Patients with HER-2 Negative Breast Cancer Especially Triple Negative Breast Cancer: A Meta-Analysis. Plos One 11(8): E0160148-E0160148, 2016

Triple negative breast cancer: new therapeutic approaches and BRCA status. Apmis 126(5): 371-379, 2018

How to integrate new drugs in the current therapeutic landscape of metastatic triple negative breast cancer. Annals of Oncology 23(Suppl 9): Ix29-Ix30, 2012

Regulation of stem cells-related signaling pathways in response to doxorubicin treatment in Hs578T triple-negative breast cancer cells. Molecular and Cellular Biochemistry 409(1-2): 163-176, 2016

Structural Variations in Selenium Drugs Determine Selective Toxicity towards Triple Negative Breast Cancer. Free Radical Biology and Medicine 112: 98-99, 2017

Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer. Molecular Cancer Therapeutics 14(8): 1824-1836, 2016

Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression. Cancer Research 76(10): 2932-2943, 2017

Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer. Oncotarget 7(27): 41559-41574, 2016

Current Status of Poly(ADP-ribose) Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer. International Journal of Breast Cancer 2012: 829315-829315, 2012

Novel therapeutic strategies in the treatment of triple-negative breast cancer. Therapeutic Advances in Medical Oncology 9(7): 493-511, 2017

Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells. International Journal of Nanomedicine 10: 3937-3953, 2016

Dynamic contrast-enhanced MRI-based biomarkers of therapeutic response in triple-negative breast cancer. Journal of the American Medical Informatics Association 20(6): 1059-1066, 2013

Qualitative and quantitative image-based biomarkers of therapeutic response in triple-negative breast cancer. AMIA Joint Summits on Translational Science Proceedings. AMIA Joint Summits on Translational Science 2013: 62-62, 2013

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer. Oncology Letters 3(1): 163-171, 2012