Endocrine Abstracts

Introduction: In endocrine tumours, such as that of the breast, the protein survivin has emerged as a unique regulator of cell death. We have previously shown that bFGF regulates survivin expression through the MAP kinase cascade. The transcriptional complex myc/max is an oncogene that lies downstream of the MAP kinase pathway suggesting a possible role in survivin's regulation.Aim: To determine if bFGF can mediate survivin expression by signalling throu...

In breast cancer associations between p160 co-activator proteins and the development of resistance to endocrine treatment have been shown. We hypothesized that nuclear co-regulatory proteins may interact with non-steroid receptors. We investigated the effect of silencing the co-activator, SRC-1, on tumour cell growth in vitro. We also examined the MAPK activated transcription factors, Ets, as possible interaction proteins of the co-activator SRC-1 in human breast cancer. The e...

The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. Steroidogenic factor 1 (SF-1), an orphan nuclear receptor is thought to be central to the transcriptional regulation of all steroid hydroxylase enzymes. Recently co-regulatory proteins have been implicated in the modulation of nuclear receptor transcriptional activity. We hypothesised that classic and novel secretogogues, including forskolin, angiote...

Introduction: Regulation of HER2 through the transcription factor PEA3 is associated with tumour progression and resistance to endocrine treatment in human breast cancer. The mechanism of this resistance remains unclear. Activation of estrogen receptor co-activator proteins via the MAP-kinase pathway is thought to be central to tamoxifen insensitivity. We hypothesised that activation of HER2 by PEA3 may result in activation of co-activator proteins such as AIB1 (amplified-in-b...

Introduction: Faslodex (Fulvestrant) is a novel antiestrogen, which has been demonstrated to have clinical efficacy in metastatic breast cancer. It is thought to mediate it's effects by downregulating ER expression. ER-alpha and ER-beta function as transcription factors to modulate genes relevant to breast cancer progression. Both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that Faslodex may modulate the recruitment and intera...

The capacity of the adrenal to produce cortisol is controlled in part by the transcription of 21 hydroxylase(CYP21) and production of androgens by 17 hydroxylase/17-20 lyase(CYP17) in response to secretogoues including ACTH, angiotensin-II(A-II) and forskolin. Both mRNA and protein expression of CYP21 was upregulated in the presence of forskolin and A-II alone and in combination in vitro H-295 adrenocortical cells, as detected by northern and western blotting. Whereas, ...

ER-alpha and ER-beta function as transcription factors to modulate expression of target genes. Both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that these co-regulators are expressed in breast cancer tissue and may be differentially regulated by estrogen and tamoxifen.ER-alpha, ER-beta, the co-activator SRC-1, and the co-repressor SMRT were localized within breast tissue by immunohistochemistry, and the spatial co-expressi...

ER-alpha and ER-beta function as transcription factors to modulate expression of target genes. Both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that these co-regulators are expressed in breast cancer tissue and may be differentially regulated by estrogen and tamoxifen.ER-alpha, ER-beta, the co-activator SRC-1, and the co-repressor SMRT were localized within breast tissue by immunohistochemistry, and the ...

The adrenal cortex produces aldosterone, cortisol and adrenal androgens. ACTH regulates the production of both cortisol and adrenal androgens. However there are physiological and pathophysiological conditions where the production of these steroids is divergent. We examined the effect angiotension II (A-II) and insulin on the relative production of cortisol and adrenal androgens in the human adrenal H-295 cell line. We determined the ability of these secretogogues to regulate t...

The adrenal cortex produces aldosterone, cortisol and adrenal androgens in response to secretogogues including ACTH, angiotensin II(A-II) and insulin. Differential regulation of adrenal steroids is through the modulation of specific key steroidogenic enzymes. The capacity of the adrenal to produce cortisol is controlled in part by the transcription of 3beta-hydroxysteroiddehydrogenase (3beta HSD) and production of adrenal androgens by 17 hydroxylase/17-20 lyase (CYP17). Protei...