A comparison of gene expression changes in response to diethylstilbestrol treatment in wild-type and p53+/− hemizygous knockout mice using focussed arrays

Salleh, Mohd Nazil; Caldwell, John; Carmichael, Paul L.

doi:10.1016/s0300-483x(02)00587-5

Cited by 12 publications

(1 citation statement)

References 30 publications

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“…Expression of genes associated with apoptosis and cell cycle have been investigated in liver of genetic manipulation in female p53 +/7 knockout mice and isogenic wild-type parent mice (12). Several reports have been published that, oestrogens induces apoptosis in murine thymocytes (13).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of p53+/‐ Knockout and Wild‐type Mice Following Diethylstilbestrol Administration

et al. 2004

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SummaryStudies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53 +/7 knockout mice and wild-type mice on the kidney and uterus of female mice. p53 +/7 knockout mice and wild-type mice were treated with DES (500 mmole kg 71 ) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkb1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53 +/7 knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53 +/7 knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53 +/7 knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53 +/7 knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.

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Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of p53+/‐ Knockout and Wild‐type Mice Following Diethylstilbestrol Administration

et al. 2004

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Gadd45 in Modulation of Solid Tumors and Leukemia

Hoffman

Liebermann

2013

Advances in Experimental Medicine and Biology

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The stress response gadd45 gene family participates in cell cycle control, cell survival, apoptosis, maintenance of genomic stability, DNA repair, and active DNA demethylation, in response to environmental and physiological stress including oncogenic stress. Given these diverse functions, it is anticipated that gadd45 genes can influence the initiation and progression of malignancy and the response to different treatments. This chapter will provide an overview of how the different members of the gadd45 gene family are expressed in different tumors and leukemia, how this may impact on progression of disease, and what happens when expression is manipulated. Studies from human tumor/leukemia samples, cell lines, and animal models are included in this review. An overriding theme is that each of the gadd45 genes has both tumor suppressor and tumor promoter functions, dependent on the tissue/cell type and transforming event.

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Induction of CYP1A1 and CYP1B1 and formation of carcinogen–DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene

et al. 2005

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A comparison of gene expression changes in response to diethylstilbestrol treatment in wild-type and p53+/− hemizygous knockout mice using focussed arrays

Cited by 12 publications

References 30 publications

Gene Expression Profiling of p53+/‐ Knockout and Wild‐type Mice Following Diethylstilbestrol Administration

Gene Expression Profiling of p53+/‐ Knockout and Wild‐type Mice Following Diethylstilbestrol Administration

Gadd45 in Modulation of Solid Tumors and Leukemia

Induction of CYP1A1 and CYP1B1 and formation of carcinogen–DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene

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