Loss of c-KIT expression in breast cancer correlates with malignant transformation of breast epithelium and is mediated by KIT gene promoter DNA hypermethylation

Experimental and Molecular Pathology
Radoslav JanostiakMalini Harigopal

Abstract

KIT Proto-Oncogene Receptor Tyrosine Kinase (KIT) is a transmembrane receptor tyrosine kinase which plays an important role in regulation of cell proliferation, survival and migration. Interestingly, the role of c-KIT in malignant transformation seems to be highly tissue-specific and it can act either as an oncogene or tumor suppressor gene. Here we analyzed the expression of c-KIT in normal breast tissues and tissues from different stages encompassing major steps of breast tumor development. Our study showed, that the c-KIT protein expression is gradually lost during the process of breast tissue transformation. The analysis of previously published datasets revealed that c-KIT expression in breast malignancies was downregulated at mRNA level. Because sequencing studies did not identify any recurrent mutations or copy number alterations, we proposed a potential epigenetic mechanism for the downregulation of c-KIT expression. In-silico analysis of the KIT promoter revealed the presence of CpG islands, therefore we performed bisulfite sequencing of normal breast epithelial tissues as well as breast tumor samples. We found, that KIT promoter is hypermethylated in breast tumors compared to normal breast tissues. Furthermore, treatme...Continue Reading

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Citations

Oct 28, 2019·Veterinary and Comparative Oncology·Yi-Chen ChenWei-Li Hsu
Oct 2, 2019·Veterinary and Comparative Oncology·Miluse VozdovaJiri Rubes
Jul 2, 2020·Yonsei Medical Journal·Duc Daniel M PhamHensin Tsao
Oct 6, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Matthew de GannesAlvaro Puga
Dec 8, 2020·Frontiers in Oncology·Asadoor Amirkhani NamagerdiAntonio Giordano
Mar 9, 2021·Frontiers in Veterinary Science·Guillermo ValdiviaLaura Peña

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