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290904 occurrences (No.84 in the rank) during 5 years in the PubMed. [no cache] 500 found

284) Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter.

--- 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.

--- ABSTRACT END ---

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(1)66 the	(12)4 activity	(24)2 among	(35)2 interhemispheric
(2)30 in	(13)4 both	(25)2 availability	(36)2 it
(3)23 by	(14)4 cell	(26)2 blood	(37)2 likelihood
(4)13 null	(16)3 ability	(27)2 but	(38)2 number
(5)13 to	(17)3 after	(28)2 compared	(39)2 rates
(6)10 glutathione	(18)3 binding	(29)2 effortful	(40)2 stem
(7)8 and	(19)3 or	(30)2 ejection	(41)2 total
(8)8 expression	(20)3 risk	(31)2 following	(42)2 tumor
(9)5 levels	(21)3 sensitivity	(32)2 from	(43)2 which
(10)5 significantly	(22)2 (P	(33)2 glutathione,
(11)4 PGE2	(23)2 BRCA-1	(34)2 hippocampal

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--- WordNet output for reduced --- =>貧しい暮らし, 落ちぶれた生活 Overview of verb reduce The verb reduce has 20 senses (first 11 from tagged texts) 1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on; make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health benefits") 2. (9) reduce -- (make less complex; "reduce a problem to a single question") 3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to slavery") 4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one term for another) 5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She reduced her niece to a servant") 6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a compromise") 7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater"; "Can you shrink this image?") 8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living") 9. (1) reduce, scale down -- (make smaller; "reduce an image") 10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with hydrogen or form a hydride, or to undergo an increase in the number of electrons) 11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners") 12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently"; "The rich landowners subjugated the peasants working the land") 13. reduce -- (undergo meiosis; "The cells reduce") 14. reduce -- (reposition (a broken bone after surgery) back to its normal site) 15. reduce -- (destress and thus weaken a sound when pronouncing it) 16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while retaining essential elements; "The manuscript must be shortened") 17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The sauce should reduce to one cup") 18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the sauce by boiling it for a long time") 19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture; "cut bourbon") 20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight) Overview of adj reduced The adj reduced has 2 senses (first 2 from tagged texts) 1. (6) decreased, reduced -- (made less in size or amount or degree) 2. (1) reduced, rock-bottom -- (well below normal (especially in price)) --- WordNet end ---