Benzo(a)pyrene, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, alters cell adhesion proteins in human uterine RL95-2 cells.
This study compared the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two aryl hydrocarbon receptor agonists, on cell attachment and adherens junction proteins in RL95-2 human uterine endometrial cells. Exposure to 10 microM BaP significantly decreased cell attachment to Matrigel, whereas 10 nM TCDD had no effect. Immunocytochemistry and Western immunoblot analysis showed that BaP, but not TCDD, produced a marked loss of plasma membrane epidermal growth factor receptor (EGF-R) localized along intercellular boundaries. BaP-treated cells exhibited significant decreases in beta-catenin and cadherin protein levels, while vinculin levels remained unchanged relative to control. In contrast, TCDD treatment had no effect on the levels of beta-catenin, cadherin, or vinculin. Further studies using the fluorescein labeled peptide phalloidin showed the presence of continuous subcortical actin filaments in control cells, whereas BaP-treated cells had subcortical actin aggregates. Thus, in contrast to TCDD, BaP produces a loss of cell attachment involving decreased localization of molecules important for cell-cell interactions in RL95-2 cells.
McGarry
Michelle A
MA
Department of Pharmacology and Therapeutics, University of Florida, P.O. Box 100267, JHMHSC, 1600 S.W. Archer Road, Gainesville, FL 32610-0267, USA.
Charles
Grantley D
GD
Medrano
Theresa
T
Bubb
Michael R
MR
Grant
Maria B
MB
Campbell-Thompson
Martha
M
Shiverick
Kathleen T
KT
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D010590:Phalloidine / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D015534:Trans-Activators; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D051176:beta Catenin
D000199:Actins; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D015534:Trans-Activators; D051176:beta Catenin; D016596:Vinculin; D010590:Phalloidine; D001564:Benzo(a)pyrene; D066246:ErbB Receptors; D004121:Dimethyl Sulfoxide