Loss of Protein Kinase Cδ/HuR Interaction Is Necessary to Doxorubicin Resistance in Breast Cancer Cell Lines

Abstract

The protein kinase Cd (PKCd) interacts with and phosphorylates

Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance

“…DNA topoisomerases, apoptosis-regulating genes, kinases, ABC transporters and autophagy regulating genes were the most frequently influenced resistance mechanisms. Down-regulated DNA topoisomerase 2 has been linked with doxorubicin resistance51. Indeed, DNA topoisomerases 2A ( TOP2A ) and 2B ( TOP2B ) were 6.8- and 2.3-fold down-regulated in CEM/ADR5000 cells, respectively.…”

Current Evidence and Future Perspectives on HuR and Breast Cancer Development, Prognosis, and Treatment

“…HuR expression has been also noted in nontumorigenic immortalized epithelial HB2 [50] and HMT-3522-T4-2 [54] cells, epithelial ductal carcinoma T47D [50] , [54] , [55] , [56] and ZR-75-1 cells [57] , epithelial carcinoma BT-20 [51] and Hs578T cells [58] , [59] , and epithelial adenocarcinoma SK-BR-3 cells [38] , [51] , [54] , [60] , [61] .…”

“…Doxorubicin treatment (10 μM) induces HuR phosphorylation and subsequent nucleocytoplasmic shuttling in MCF7 cells and promotes HuR binding to its targets, such as c-fos, c-myc, and SOCS3 [79] . More specifically, doxorubicin activates protein kinase C delta, which phosphorylates HuR on serines 221 and 318 [46] , [61] . In contrast, HuR protein levels are reduced in doxorubicin-resistant MCF7 and MBA-MD-231 cells, and HuR cellular localization is not affected by doxorubicin treatment in MCF7 doxorubicin-resistant cells [79] .…”

Η Κλινική Σημασία Της Έκφρασης Της Πρωτεΐνης HUR Στον Καρκίνο Του Μαστού

“…Έκφραση της πρωτεΐνης HuR έχει επίσης περιγραφεί στις μη-καρκινικές κυτταρικές σειρές του μαστού HB2 (Leandersson, K, et al 2006) και HMT-3522-T4-2 (Guo X, et al 2009), καθώς και στις λιγότερο χρησιμοποιούμενες κυτταρικές σειρές καρκινώματος του μαστού T47D (Leandersson, K, et al 2006;Guo X, et al 2009;Meng, Z., et al, 2008;Saunus JM, et al 2008) και ZR-75-1 (Yuan Z, et al, 2011), BT-20 (Woo, H.H., et al, 2009), Hs578T (Suswam EA, et al, 2005;Gabai, V.L., et al, 2012) και SK-BR-3 (Scott GK, et al, 2008;Woo, H.H., et al, 2009;Guo X, et al 2009;Chock K, et al2010;Latorre E, et al, 2014).…”

“…Τα επίπεδα του αναστολέα THBS1 στο πλάσμα, συσχετίζονται θετικά με την εξέλιξη του καρκίνου του μαστού (Luo NA, et al,2014). Η πρωτεΐνη HuR προσδένεται στην τελική 3'-UTR του THBS1 mRNA στα κύτταρα των κυτταρικών σειρών MCF10A και MDA-MB-231, επηρεάζοντας τα επίπεδα έκφρασης της πρωτεΐνης THBS1 (Suswam EA, et al, 2005;Latorre E, et al, 2014 (Suswam EA, et al, 2005 (Luo NA, et al, 2014).…”