Phosphorylated ribosomal S6 (p-rpS6) as a post-treatment indicator of HER2 signalling targeted drug resistance.
OBJECTIVE
To identify clinically relevant predictive biomarkers of trastuzumab resistance.


METHODS
MTT, FACS assays, immunoblotting and immunocytochemistry were used to phenotypically characterize drug responses of two cell models BT474R and SKBR3R. Student's t-test and Spearman's correlation were applied for statistic analysis.


RESULTS
The activity of a downstream effector of the HER2 pathway phosphorylated ribosomal protein S6 (p-rpS6), was suppressed by trastuzumab in the parental cell lines yet remained unchanged in the resistant cells following treatment. The level of p-rpS6 was inversely correlated to the drug induced growth inhibition of trastuzumab-resistant cells when they are treated with selected HER2 targeting drugs.


CONCLUSIONS
p-rpS6 is a robust post-treatment indicator of HER2 pathway-targeted therapy resistance.
a Department of Medicine , Norris Comprehensive Cancer Center, University of Southern California , Los Angeles , CA , USA .
Gloria
G
Yang-Kolodji
Shannon M
SM
Mumenthaler
Arjun
A
Mehta
Lingyun
L
Ji
Debu
D
Tripathy
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D015398:Signal Transduction; D000068878:Trastuzumab / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015415:Biomarkers; D018719:Erb-b2 Receptor Tyrosine Kinases; D038601:Ribosomal Protein S6; D000068878:Trastuzumab
Biomarker; breast cancer; cell model; drug response; trastuzumab resistance