* Growth factor receptor/steroid receptor cross talk in trastuzumab-treated breast cancer.
- Treatment with tyrosine kinase inhibitors (TKIs) including trastuzumab has revolutionized the management of HER2-positive breast cancer. Recent evaluation of clinical trial data suggests that a subset of HER2/ER double-positive cancers may not receive significant benefit from the TKI therapy. Here we investigate the cross talk between HER2 and ER in breast cancer and monitor the effect of trastuzumab on the tyrosine kinase effector transcription factor Myc. In HER2-positive breast cancer patients treated with neoadjuvant trastuzumab, steroid receptor-negative status (ER and PR negative) of pre-treatment biopsies predicted pathological complete response (pCR) (n=31 patients, P=0.0486), whereas elevated Myc protein inversely associated with pCR (P=0.0446). Liquid chromatography mass spectrometry identified the corepressor SMRT as a novel Myc-interacting protein. Trastuzumab treatment enhanced Myc-SMRT interactions in HER2-overexpressing breast cancer cells (LCC1) and inhibited expression of the Myc target gene survivin. In HER2-low, ER-positive steroid-dominant cells (MCF7), trastuzumab therapy repressed Myc-SMRT interactions and upregulated survivin expression. Trastuzumab treatment induced ER-CBP interactions, enhanced ER transcriptional activity and upregulated expression of the ER target gene pS2. The absence of pS2 expression in pre-treatment biopsies predicted pCR to neoadjuvant trastuzumab in breast cancer patients (n=25, P=0.0089) and pS2 expression associated with residual cancer burden (P=0.0196). Furthermore, metastatic tissues from patients who had failed trastuzumab therapy were pS2 positive. In HER2-overexpressing cells, trastuzumab treatment can repress Myc transcriptional activity and clinical response is favorable. However, with co-expression of the steroid pathway, this inhibition is lost and response to treatment is often poor.
=>反応, 応答, 返答, 返報, 反響, 答唱句
Overview of noun response
The noun response has 7 senses (first 5 from tagged texts)
1. (11) response -- (a result; "this situation developed in response to events in Africa")
2. (11) reaction, response -- (a bodily process occurring due to the effect of some antecedent
stimulus or agent; "a bad reaction to the medicine"; "his responses have slowed with age")
3. (6) answer, reply, response -- (a statement (either spoken or written) that is made to reply to a
question or request or criticism or accusation; "I waited several days for his answer"; "he wrote
replies to several of his critics")
4. (4) reception, response -- (the manner in which something is greeted; "she did not expect the
cold reception she received from her superiors")
5. (1) response -- (a phrase recited or sung by the congregation following a versicle by the priest
or minister)
6. reply, response -- (the speech act of continuing a conversational exchange; "he growled his
reply")
7. response -- (the manner in which an electrical or mechanical device responds to an input signal
or a range of input signals)
--- WordNet end ---