PubMed:15585645 JSON TXT

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Id	Subject	Object	Predicate	Lexical cue
T0	143-152	gene:595	denotes	cyclin D1
T1	162-178	disease:C0006142	denotes	breast carcinoma
T2	143-152	gene:595	denotes	cyclin D1
T3	162-178	disease:C0678222	denotes	breast carcinoma
R1	T0	T1	associated_with	cyclin D1,breast carcinoma
R2	T2	T3	associated_with	cyclin D1,breast carcinoma

Id	Subject	Object	Predicate	Lexical cue
15585645-0#55#72#gene2099	55-72	gene2099	denotes	estrogen receptor
15585645-0#143#152#gene595	143-152	gene595	denotes	cyclin D1
15585645-0#162#178#diseaseC0678222	162-178	diseaseC0678222	denotes	breast carcinoma
15585645-1#0#17#gene2099	200-217	gene2099	denotes	Estrogen receptor
15585645-1#43#56#diseaseC0006142	243-256	diseaseC0006142	denotes	breast cancer
55#72#gene2099162#178#diseaseC0678222	15585645-0#55#72#gene2099	15585645-0#162#178#diseaseC0678222	associated_with	estrogen receptor,breast carcinoma
143#152#gene595162#178#diseaseC0678222	15585645-0#143#152#gene595	15585645-0#162#178#diseaseC0678222	associated_with	cyclin D1,breast carcinoma
0#17#gene209943#56#diseaseC0006142	15585645-1#0#17#gene2099	15585645-1#43#56#diseaseC0006142	associated_with	Estrogen receptor,breast cancer

Id	Subject	Object	Predicate	Lexical cue
T1	200-525	OBJECTIVE	denotes	Estrogen receptor alpha (ERalpha)-positive breast cancer cell lines are up to 10 times more sensitive than ERalpha-negative cell lines to the antiproliferative activity of the histone deacetylase inhibitor trichostatin A (TSA). The purpose of the study was to investigate the mechanisms underlying this differential response.
T2	559-1169	RESULTS	denotes	In the ERalpha-positive MCF-7 cell line, TSA repressed ERalpha and cyclin D1 transcription and induced ubiquitin dependent proteasomal degradation of cyclin D1, leading primarily to G(1)-S-phase cell cycle arrest. By contrast, cyclin D1 degradation was enhanced but its transcription unaffected by TSA in the ERalpha-negative MDA-MB-231 cell line, which arrested in G(2)-M phase. Cyclin D1 degradation involved Skp2/p45, a regulatory component of the Skp1/Cullin/F-box complex; silencing SKP2 gene expression by RNA interference stabilized cyclin D1 and abrogated the cyclin D1 down-regulation response to TSA.
T3	1183-1603	CONCLUSIONS	denotes	Tamoxifen has been shown to inhibit ERalpha-mediated cyclin D1 transcription, and acquired resistance to tamoxifen is associated with a shift to ERalpha-independent cyclin D1 up-regulation. Taken together, our data show that TSA effectively induces cyclin D1 down-regulation through both ERalpha-dependent and ERalpha-independent mechanisms, providing an important new strategy for combating resistance to antiestrogens.