Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements

Oncogene
Y MizumotoT Kiyono

Abstract

Several genetic mutations have been identified in human endometrial cancers, but the specific combinations of mutations required to form endometrial cancer cells remain unknown. In the present study, we established an in vitro model of endometrial carcinogenesis, in which defined genetic elements were introduced into endometrial epithelial cells to create transformed endometrial cells at different stages. Introduction of the human papillomavirus type 16 E6/E7 gene and the human telomerase reverse transcriptase (hTERT) gene into human primary endometrial epithelial cells was sufficient to generate immortalized cells. Introduction of hTERT in early passages stabilized telomeres and created immortalized cells with normal karyotype, whereas introduction of hTERT in later passages generated immortalized cells but with widespread chromosome abnormalities. However, neither of those two immortalized cell lines exhibited tumorigenic phenotypes. Tumorigenic endometrial epithelial cells with invasive capacity were created by introducing a mutant K-ras allele into immortalized cells, keeping their chromosomes intact. Inhibiting the PTEN gene and activating Akt pathways did not create tumorigenic phenotypes, although the latter conferred an...Continue Reading

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Citations

Jan 19, 2012·Molecular Cancer Research : MCR·Katherine B ChiappinelliPaul J Goodfellow
Aug 15, 2013·International Journal of Molecular Sciences·Yan YinLiang Ma
Jul 15, 2011·Stem Cell Reviews and Reports·Ji-Seon LeeHyuk Jin Cha
Jul 18, 2015·FEBS Letters·Tomohiko FukudaTomoyuki Fujii
Jun 26, 2012·International Journal of Cancer. Journal International Du Cancer·Takuhei YokoyamaTetsuji Naka
Nov 19, 2014·PloS One·Amie J RadenbaughDavid Haussler
Oct 15, 2013·PloS One·Chandrani MukhopadhyayMayumi Naramura
Jun 6, 2013·PloS One·Kathrin S ZellerStaffan Johansson
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Nov 28, 2006·Trends in Cell Biology·Rafael García-Mata, Keith Burridge
Dec 25, 2013·International Journal of Oncology·Mitsuhiro NakamuraSatoru Kyo
Dec 7, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Satoru KyoMasaki Inoue
Mar 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yasunari MizumotoMasaki Inoue
Jul 18, 2008·Cancer Research·Mako Narisawa-SaitoTohru Kiyono

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