ELIZA

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286252 occurrences (No.88 in the rank) during 5 years in the PubMed. [no cache] 500 found

64) Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD).

--- ABSTRACT ---

PMID:24469035 DOI:10.1038/onc.2013.579

2015 Oncogene

* Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes.

- Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.

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(1)55 the	(15)3 key	(29)2 P-selectin,	(44)2 cell
(2)11 a	(16)3 multiple	(30)2 P2X3	(45)2 constitutively
(3)9 genes	(17)3 ncRAN	(32)2 Sema	(46)2 hyaluronan
(4)8 several	(18)3 nicotine-induced	(33)2 Siglec-9	(47)2 imprinted
(5)6 miR-218	(19)3 nuclear	(34)2 TAF4	(48)2 intercellular
(6)5 these	(20)3 specific	(35)2 Wnt	(49)2 membrane
(7)4 VEGF	(21)3 this	(36)2 acetyl-CoA	(50)2 miR-128
(8)4 first	(22)2 AdipoR1	(37)2 adhesion	(51)2 napsin
(9)4 matrix	(23)2 Caspase	(38)2 adiponectin	(52)2 phosphorylated
(10)3 CYP1A1	(24)2 FBP1	(39)2 angiogenic	(53)2 piRNA-823
(11)3 DNMT1	(25)2 GABAA	(40)2 anti-apoptotic	(54)2 pro-inflammatory
(12)3 all	(26)2 GLP-1R	(41)2 b-FGF,	(55)2 some
(13)3 cardiac	(27)2 Ki-67,	(42)2 c-Myc	(56)2 three
(14)3 integrin	(28)2 LOX-1	(43)2 cartilage

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--- WordNet output for expression --- =>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情 Overview of noun expression The noun expression has 9 senses (first 6 from tagged texts) 1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's face; "a sad expression"; "a look of triumph"; "an angry face") 2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an expression of grief"; "the pulse is a reflection of the heart's condition") 3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my ideas"; "the idea was immediate but the verbalism took hours") 4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular situations; "pardon the expression") 5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better formulation"; "his manner of expression showed how much he cared") 6. (4) formula, expression -- (a group of symbols that make a mathematical statement) 7. expression -- ((genetics) the process of expressing a gene) 8. construction, grammatical construction, expression -- (a group of words that form a constituent of a sentence and are considered as a single unit; "I concluded from his awkward constructions that he was a foreigner") 9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk from her breast") --- WordNet end ---