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Hemin inhibits cyclin D1 and IGF-1 expression via STAT5b under hypoxia in ER alpha-negative MDA-MB 231 breast cancer cells

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Authors
Lim, Eun-Joung; Joung, Youn-Hee; Jung, Se-Mi; Park, Se Hyung; Kim, Sang Yoon; Hong, Dae Young; Ye, Sang-Kyu; Park, Eui U.; Chung, Ill-Min; Yang, Young Mok; Park, Taekyu; Moon, Eon-Soo; Chung, So Chung; Hwang, Tae Sook; Park, Jin Hee
Issue Date
2010-05
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF ONCOLOGY; Vol.36 5; 1243-1251
Keywords
hemincyclin D1MDA-MB 231binding sitegene expressionbreast cancer cellsIGF-IRhypoxiaSTAT5bIGF-1
Abstract
Cychn D1 and insulin-like growth factor 1 receptor (IGE-IR) are key regulators of cell proliferation that are overexpressed in most breast cancers The purpose of the present study was to investigate the molecular mechanism by which hemin exerts its inhibitory effects on aggressive breast cancer cells We found that hemin regulates cychn DI and ICE-I R proteins and insulin-like growth factor-1 gene expression through STAT5b in breast cancer cells. We confirmed that STAT5b. cyclin DI. and IGE-1R is up-regulated by hypoxia. and the increased sTAT5b binds strongly to the STAT5-binding sites contained within the distal 5-flanking region of IGE-1 acne in breast cancer cells EMSA studies showed that S1`AT5 binding activity to the IGE-1 and cychn DI promoter was distinctly decreased by hemin in STAT5b-transfected COS-7 or MDA-MB 231 cells. IGE-1 gene expression was also decreased by hemin in mammary epithelial cells STAT5b expression was inhibited in sr RNA experiments and by hermit. leadma to decreased levels of IGE-1 These results provide a basis for molecular targets in cancer treatment via the STAT5b/IGE-1 or /cychn DI pathway in solid tumor cells These data indicate that hem in inhibits the cyclin D1 and IGE-1 expression via STAT5b under hypoxia in ER alpha-negative breast cancer cells These findings are valuable toward understanding the role of hemin-induced inhibition of cyclin D1 and IGF-1 expression under hypoxia in Invasive and metastatic breast cancer
ISSN
1019-6439
Language
English
URI
http://hdl.handle.net/10371/78072
DOI
https://doi.org/10.3892/ijo_00000608
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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