Changes in the distribution pattern of Claudin tight junction proteins during the progression of XXXX skin tumorigenesis.

@entity3653 @entity70762 @entity14160 @entity19 @entity5 @entity1489 @entity5168 @entity1324 @entity41911 @entity70763 @entity106 @entity865 @entity8840 @entity70761 @entity864
BACKGROUND: Despite the fact that morphological and physiological observations suggest that the tight junction (TJ)-based permeability barrier is modified/disrupted in tumorigenesis, the role of members of the Claudin (Cldn) family of TJ proteins is not well-understood. Using a well-established two-stage chemical carcinogenesis model, we investigated the temporal and spatial changes in expression of those Cldns that we have previously demonstrated to be important in epidermal differentiation and the formation of the epidermal permeability barrier, i.e., @entity8840 , @entity70761 , @entity41911 , @entity70762 and @entity70763 . METHODS: The lower dorsal backskin of @entity19 was treated topically with @entity3653 ( @entity106 ; 0.25 mg/ml in @entity1324 ) and following a 10-day incubation period, @entity864 ( @entity865 ; 25 microg/ml in @entity1324 ) was applied three times a week to the same area. Backskin samples were dissected 2, 4, 6, 8 and 12 weeks after the initiation of the experimental protocol and immunohistochemistry was performed on sections using antibodies against the following: @entity8840 , @entity70761 , @entity41911 , @entity70762 , @entity70763 , @entity14160 and @entity5168 . RESULTS: Our data indicate that along with the changes in epidermal cell morphology and differentiation that occur during @entity5 formation, there is a dramatic change in Cldn distribution consistent with cell polarity and barrier selectivity changes. Specifically, in the early stages of @entity106 / @entity865 treatment, the suprabasal-specific Cldns occupy an expanded zone of expression corresponding to an increased number of suprabasal epidermal cell layers. As tumorigenesis progressed, the number of suprabasal epidermal layers positive for @entity70761 , @entity41911 , @entity70762 and @entity70763 was reduced, especially in the lower strata of the expanded suprabasal zone. In addition, a variably reduced cell membrane association of those differentiation-specific Cldns was observed, especially within the infiltrating epidermal structures. In contrast, @entity8840 (which is normally expressed in all the living layers of the epidermis) remained restricted to the cell membrane throughout the tumorigenesis protocol. However commencing 2 weeks after treatment there was a marked decrease in the number of @entity8840 -positive basal cells, and the zone of @entity8840 -null epidermal cells was expanded up into the lower stratified epidermis throughout the progression of @entity106 / @entity865 treatment. In addition, there was no @entity8840 localization in the infiltrating epidermal structures of the tumorigenic epidermis. CONCLUSION: This is the first demonstration of the changes in Cldn expression in the progression of @entity106 / @entity865 -induced @entity1489 ; however further investigation into the molecular mechanisms regulating the observed changes in barrier selectivity during tumorigenesis is required.
