Proliferation and apoptosis in PhIP-induced rat mammary gland carcinomas with elevated phosphotyrosine-STAT5a.

In the present study we addressed whether proliferation and apoptosis in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland carcinomas were different between carcinomas with high and low expression of phosphotyrosine (pY)-STAT5a. We determined that carcinomas with high pY-STAT5a were more proliferative (MIB5 immunostaining) and had a higher expression of cyclin D1 and estrogen receptor alpha. Furthermore, carcinomas with elevated pY-STAT5a demonstrated lower apoptosis as measured by the TUNEL assay and the Bcl-2 to Bax ratio, and showed increased expression of the long and short isoforms of the prolactin receptor.

Gene expression profiling in the mammary gland of rats treated with 7,12-dimethylbenz[a]anthracene.

Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed.

Mercury, cadmium, and arsenite enhance heat shock protein synthesis in chick embryos prior to embryotoxicity.

Background: Cells respond to adverse environmental stimuli by enhancing the expression of specific genes, the products of which include a suite of proteins known as heat shock proteins (hsps), a response often attributed to cellular protection.

Methods: In this study, we characterized alterations in hsp expression in chick embryos (Hamburger-Hamilton stage 17, 72 h) exposed in ovo to arsenite (As), mercury (Hg), and cadmium (Cd), known developmental toxicants. Embryos were incubated for 2 h following exposure to 3, 10, 30, or 100 nmol metal, or for 2, 4, 12, or 24 h following treatment with 10 nmol metal.

Regulation of uterine hsp90alpha, hsp72 and HSF-1 transcription in B6C3F1 mice by beta-estradiol and bisphenol A: involvement of the estrogen receptor and protein kinase C.

We have previously demonstrated that bisphenol A (BPA)- and beta-estradiol (E2)-induced increases in uterine weight and heat shock protein (hsp) 90alpha and hsp72 levels are mediated through the estrogen receptor (ER). It is not, however, clear if BPA and E2 regulation of hsps is at the transcriptional or post-transcriptional level. Therefore, in this study we examined the ability of BPA and E2 to increase uterine weight and regulate transcription of these hsps and of heat shock factor (HSF)-1 in ovariectomized B6C3F1 mice at 6 or 24 h after a single subcutaneous injection of E2 (1 microg/kg) or BPA (100 mg/kg).

Effects of 17 alpha-methyltestosterone on uterine morphology and heat shock protein expression are mediated through estrogen and androgen receptors.

Testosterone and the synthetic androgen, 17 alpha-methyltestosterone (MT), have been shown to increase uterine weights and alter uterine morphology. However, whereas the mechanism of action of testosterone in the uterus has been studied, it is not known if the actions of MT are mediated through androgen (AR) or estrogen (ER) receptors. In the present study, we have shown that MT, at 0.

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown that bisphenol A (BPA), similarly to 17ss-estradiol (E2), increases levels of uterine heat shock proteins (hsps), mainly hsp90alpha and glucose-regulated protein (grp) 94. In this study we investigated whether increases in uterine hsp levels are a specific response of estrogens or estrogen mimics.