Papillomavirus E6 oncoprotein up-regulates occludin and ZO-2 expression in ovariectomized mice epidermis.
We have studied the expression of the tight junction proteins (TJ) occludin, claudin-1 and ZO-2 in the epidermis of female mice. We observed a peak of expression of these proteins at postnatal day 7 and a decrease in 6 week-old mice to values similar to those found in newborn animals. We explored if the expression of the E6 oncoprotein from high-risk human papilloma virus type 16 (HPV16) in the skin of transgenic female mice (K14E6), altered TJ protein expression in a manner sensitive to ovarian hormones. We observed that in ovariectomized mice E6 up-regulates the expression of occludin and ZO-2 in the epidermis and that this effect was canceled by 17β-estradiol. Progesterone instead induced occludin and ZO-2 over-expression. However, the decreased expression of occludin and ZO-2 induced by 17β-estradiol in the epidermis was not overturned by E6 or progesterone. In addition, we employed MDCK cells transfected with E6, and observed that ZO-2 delocalizes from TJs and accumulates in the cell nuclei due to a decrease in the turnover rate of the protein. These results reinforce the view of 17β-estradiol and E6 as risk factors for the development of cancer through effects on expression and mislocalization of TJ proteins.
Department of Genetics and Molecular Biology, Center for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
Jesús
J
Hernández-Monge
Erika
E
Garay
Arturo
A
Raya-Sandino
Orlando
O
Vargas-Sierra
José
J
Díaz-Chávez
Marco
M
Popoca-Cuaya
Paul F
PF
Lambert
Lorenza
L
González-Mariscal
Patricio
P
Gariglio
D000818:Animals; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004817:Epidermis / Q000378:metabolism*; D004958:Estradiol / Q000172:deficiency; D005260:Female; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008822:Mice, Transgenic; D062793:Occludin / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D011374:Progesterone / Q000172:deficiency; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D062827:Zonula Occludens-2 Protein / Q000235:genetics / Q000378:metabolism*
D062445:Claudin-1; C068651:E6 protein, Human papillomavirus type 16; D062793:Occludin; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D062827:Zonula Occludens-2 Protein; D011374:Progesterone; D004958:Estradiol
E6; Epidermis; Estrogen; HPV; MDCK; Progesterone; Tight junction