Common and distinct mechanisms of different redox-active carcinogens involved in the transformation of mouse JB6P+ cells.

Abstract:

:We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (approximately six folds) in soft agar as compared to their JB6P+ parent cells and were associated with increased intracellular reactive oxygen species (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors that are rapidly activated by elevated intracellular ROS levels, and their composition is important in the process of cellular transformation and/or tumor progression. To investigate if carcinogenesis induced by distinct carcinogens was via similar molecular mechanisms in these transformants, gel mobility shift and immunoblot analyses were utilized to determine the distinct AP-1 compositions. Compared to parent JB6P+ cells, the gain of JunB and Fra-1 in AP-1 DNA binding complexes was markedly increased in all transformed cells, which might contribute to a more proliferative phenotype, while loss of Fra-2 occurred in JB6P+/H(2)O(2) and JB6P+/Cd cells. Differential AP-1 components in the transformants suggested that their transformations might be mediated by distinct transcription signalings with distinct AP-1 dimer compositions. However, all three transformants exhibited increased activation of pathways involved in cell proliferation (ERK/Fra-1/AP-1 and JNK/c-jun/AP-1) and anti-apoptosis (Bcl-xl). The development of the JB6P+ transformants (JB6P+/UVB; JB6P+/H(2)O(2); JB6P+/Cd) provides a unique tool to study the mechanisms that contribute to different redox-active carcinogens in a single model.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Yang S,Misner B,Chiu R,Meyskens FL Jr

doi

10.1002/mc.20410

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

485-91

issue

7

eissn

0899-1987

issn

1098-2744

journal_volume

47

pub_type

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