Human KIT ligand promoter is positively regulated by HMGA1 in breast and ovarian cancer cells

Oncogene
Nathan R TreffR Reeves

Abstract

KIT ligand (KL) and its receptor, c-kit, are coexpressed in many types of cancer cells and have been implicated in tumor growth and angiogenesis. While Sertoli cell-specific regulation of the KL promoter has been well characterized, regulation in cancer cells remains to be elucidated. We recently reported microarray results demonstrating that increased high-mobility group (HMG) A1a protein expression correlates with increased KL transcription in MCF-7 human breast cancer cells. Sequence analysis indicates a potential for multiple HMGA1 binding sites within the human KL promoter. In order to better define the underlying molecular mechanisms that HMGA1 uses to facilitate malignant transformation of cancer cells, we have used a variety of methods to determine whether HMGA1a directly regulates the human KL promoter in breast and ovarian cancer cells. Our results indicate that: (i) KL promoter activity is significantly higher in MCF-7 cells overexpressing HMGA1a; (ii) HMGA1a protein binds to AT-rich regions of the KL promoter DNA both in vitro and in vivo; (iii) mutation of the AT-rich regions inhibits HMGA1a binding in vitro; and (iv) HMGA1a-specific inhibition significantly decreases transcription of KL in OCC1 human ovarian cance...Continue Reading

References

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Citations

Jun 10, 2011·Molecular and Cellular Biochemistry·Yunzhi ZhangShilin Li
May 17, 2005·Experimental Cell Research·Gregory A DementRaymond Reeves
Aug 23, 2011·Biochemistry·Austin E Smith, Karen L Buchmueller
Aug 19, 2009·Molecular and Cellular Biology·Li MaoRaymond Reeves
Nov 12, 2009·Molecular Cancer Research : MCR·Joelle HillionLinda M S Resar
Dec 4, 2009·PloS One·Takayuki ManabeMasaya Tohyama
Feb 18, 2006·European Journal of Pharmacology·Laurent ReberNelly Frossard
Aug 17, 2005·Current Opinion in Genetics & Development·Marco E Bianchi, Alessandra Agresti
Nov 23, 2006·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Siong-Seng LiauEdward E Whang
Jan 8, 2019·Journal of Cellular and Molecular Medicine·Yuhong WangLingchuan Guo
Oct 18, 2012·Physiological Reviews·Johan Lennartsson, Lars Rönnstrand
Feb 20, 2016·Oncotarget·Marco De MartinoFrancesco Esposito
Jun 7, 2019·International Journal of Molecular Sciences·Beatrice SenigagliesiRiccardo Sgarra
Mar 17, 2006·Cancer Research·Francesco FrascaGuidalberto Manfioletti

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