A multifunctional transcription factor (A1p145) regulates the smooth muscle phenotype in mesangial cells
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Takeoka, H; Iehara, N; Uematsu-Yanagita, M; Abe, H; Sunamoto, M; Yamada, Y; Kita, T; Doi, T
Abstract
Alp145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA binding for several other genes. To elucidate the mechanisms underlying the differentiation process of mesangial cells (MCs), we investigated the effects of Alp145 on rat MCs. Cells in the early passages showed a smooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle a-actin (SMA). Cells in the late passages lost their phenotype. The amount of binding activity to COL4 promoter was inversely correlated with the level of COL4 mRNA. Introduction of antisense for Alp145 into late passage cells enhanced the levels of mRNA for COL4 and SMA. The levels of proliferating cell nuclear antigen mRNA were also suppressed. These results suggest that Alp145 is a negative transcription factor for COL4 and may be a phenotypic modulator. (C) 1998 Academic Press.
In vivo Survivors of Transformed Mouse Ovarian Surface Epithelial Cells Display Diverse Phenotypes for Gene Expression and Tumorigenicity
TUMOR BIOLOGY
Authors: Li, Xiao-Lin; Zhang, Dong-Qing; Wang, David; Knight, David S.; Yin, Lija; Bao, Jianxiong; Liu, Yong-Yu; Glass, Jonathan; Mathis, J. Michael; Zhang, Qian-Jin
Abstract
Ovarian cancer is the fifth most common cause of cancer death in women. Due to a lack of appropriate animal models, studies involving tumorigenicity, tumor progression and immune response at the molecular level are limited. We isolated many clones derived from the survivors of a transformed mouse ovarian epithelial cell line IG-10 in immune-competent mice and found that the clones displayed diverse phenotypes. Most clones were deficient in components of the MHC-I antigen presentation pathway. Soft-agarose colony assays showed different growth rates among clones. However, this did not completely correlate with each clone's in vivo tumorigenicity regarding growth, tumor mass and ascites formation, suggesting the possibility that the clones may display contrasting intrinsic gene expression. We therefore performed two types of arrays to evaluate gene expression at transcriptional and translational levels. The results showed differences in expression of COL4 alpha 5, NOS-2, and SOCS-1 genes at the transcriptional level, MIP-2 gene at the protein level and CCL5, CXCL-10, IL-1 alpha genes at both transcriptional and protein levels between low and high tumorigenic clones. Thus, our animal cell model together with the identified genes may provide a useful tool to study ovarian cancer immune response, tumorigenicity and tumor-host cell interactions in the tumor microenvironment. Copyright (C) 2008 S. Karger AG, Basel