Abstract
The human epidermal growth factor receptor 2 (HER2)‑targeting agent, lapatinib, combined with oral fluoropyrimidine capecitabine, has been previously demonstrated to be an effective treatment option for patients with trastuzumab‑resistant HER2‑positive metastatic breast cancer. To investigate the molecular mechanisms associated with the interactions between lapatinib and capecitabine, the effect of treatment with lapatinib and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) inhibitors on the expression of E2F transcription factor 1 (E2F1) and thymidylate synthase (TS), which is associated with an increased response to 5‑fluorouracil (5‑FU)‑based chemotherapy, was determined in HER2‑positive breast cancer cells. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that administration of lapatinib and PI3K inhibitors decreased the mRNA expression of TS and E2F1, a transcription factor that promotes TS gene expression, in SKBR3 and T47D cell lines. Furthermore, treatment with lapatinib and PI3K inhibitors also suppressed the mRNA expression of ribonucleotide reductase M1 subunit (RRM1), an important determinant of gemcitabine resistance, and DNA topoisomerase II‑α (TOP2A), a molecular targ...Continue Reading
References
Jan 9, 1987·Science·D J SlamonW L McGuire
Jan 1, 1984·Advances in Enzyme Regulation·T C Chou, P Talalay
Aug 1, 1995·Molecular and Cellular Biology·J DeGregoriJ R Nevins
Dec 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P G JohnstonC J Allegra
Mar 15, 2001·The New England Journal of Medicine·D J SlamonL Norton
Jan 26, 2002·Oncology·M BlacksteinA Melemed
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Timothy C Hallstrom, Joseph R Nevins
Nov 18, 2003·Journal of Human Genetics·Kohichiroh YasuiJohji Inazawa
Sep 29, 2006·The EMBO Journal·Kang LiuWeei-Chin Lin
Dec 29, 2006·The New England Journal of Medicine·Charles E GeyerDavid Cameron
Sep 23, 2008·Clinical Therapeutics·Patrick J Medina, Susan Goodin
Apr 29, 2010·Molecular Cancer Therapeutics·Junko TanizakiKazuhiko Nakagawa
Mar 8, 2011·Molecular BioSystems·Natalie LudygaMichaela Aubele
Dec 14, 2011·The New England Journal of Medicine·José BaselgaUNKNOWN CLEOPATRA Study Group
Jan 13, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Nov 20, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G CuriglianoUNKNOWN ESMO Guidelines Working Group
Feb 6, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sara A HurvitzEdith A Perez
Jan 7, 2016·PloS One·Daphne Gschwantler-KaulichChristian F Singer