IGFBP-2 expression in MCF-7 cells is regulated by the PI3K/AKT/mTOR pathway through Sp1-induced increase in transcription.

Insulin-like growth factor binding protein 2 (IGFBP-2) has been implicated in the pathophysiology of neoplasia. The PI3K/AKT/mTOR pathway has recently been shown to be a predominant regulator of IGFBP-2 at the protein level in MCF-7 breast cancer cells. However, there are gaps in knowledge with respect to the molecular mechanisms that underlie this regulation.

Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells.

To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis, cell survival, cell adhesion and motility, signal transduction, and transcription regulation.

Correlation between the presence of high-risk human papillomaviruses and Id gene expression in Syrian women with cervical cancer.

Infection by high-risk human papillomaviruses (HPVs) is considered to be the central cause of invasive cervical cancer. Previously reported studies have shown that Id genes regulate cell invasion and metastasis in several human carcinomas including cervical cancer. In order to investigate the correlation between high-risk HPVs and Id genes in human cervical cancer, the presence of high-risk HPVs and their association with Id gene expression was examined using PCR methods and tissue microarray analyses in a cohort of 44 cervical cancer patients from Syria.

PTEN genomic deletion is associated with p-Akt and AR signalling in poorer outcome, hormone refractory prostate cancer.

PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non-metastatic human HRPC tissues.

Fascin regulates prostate cancer cell invasion and is associated with metastasis and biochemical failure in prostate cancer.

Purpose: Prostate cancer metastasis to secondary organs is considered an initial event in the development of hormone refractory disease and remains the major cause of death among prostate cancer patients. In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression.

Experimental Design: Fascin protein expression was examined by immunohistochemistry in a cohort of 196 patients with localized prostate cancer and across several stages of disease progression, including hormone refractory disease.

TMPRSS2-ERG fusion is frequently observed in Gleason pattern 3 prostate cancer in a Canadian cohort.

Purpose: TMPRSS2-ERG gene fusion was recently reported as the most common gene rearrangement in prostate cancer (PCA).

Results: In this cohort 41% of the patients showed positive gene fusion status in their PCA. The TMPRSS2-ERG gene fusion status was homogenous within the same cancer focus and 82% of fusion positive PCA were present in GS 6 or 7 vs.

Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness.

Early cancer cell migration and invasion of neighboring tissues are mediated by multiple events, including activation of focal adhesion signaling. Key regulators include the focal adhesion kinase (FAK) and FAK-related proline-rich tyrosine kinase 2 (Pyk2), whose distinct functions in cancer progression remain unclear. Here, we compared Pyk2 and FAK expression in breast cancer and their effects on ErbB-2-induced tumorigenesis and the potential therapeutic utility of targeting Pyk2 compared with FAK in preclinical models of breast cancer.

High-risk HPV/ErbB-2 interaction on E-cadherin/catenin regulation in human carcinogenesis.

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with more than 120 different types identified to date. HPVs are classified as high- or low-risk (HR or LR) depending on their potential to induce cancer. Persistent infections with HR types of HPVs present a major risk factor for the development of a variety of human cancers including cervical, colorectal, head and neck as well as breast cancers.

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study.

High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis.

Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women.

Background: PALB2 has recently been identified as a breast cancer susceptibility gene. PALB2 mutations are rare causes of hereditary breast cancer but may be important in countries such as Finland where a founder mutation is present. We sought to estimate the contribution of PALB2 mutations to the burden of breast cancer in French Canadians from Quebec.

Expression of 11 beta-hydroxysteroid dehydrogenase type 1 in alveolar epithelial cells in rats.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) behaves predominantly as an oxoreductase converting the receptor-inactive glucocorticoids to their active forms in vivo, while the type 2 isoform (11beta-HSD2) possesses only dehydrogenase activity and inactivates cortisol in human or corticosterone in rat. We determined enzyme activity of 11beta-HSD in rat lungs from fetus to adult, and examined whether 11beta-HSD1 exists in alveolar type II cells, the most important site for the synthesis of pulmonary surfactant in mature lungs, by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Enzyme activity of 11beta-HSD1 and 2 in lung tissue homogenate were determined as NADP(+)- and NAD(+)-dependent conversion of corticosterone to 11-dehydrocorticosterone, respectively.

Sex steroid receptors in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase-PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERalpha, ERbeta, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients.

Steroid sulfatase and estrogen sulfotransferase in the atherosclerotic human aorta.

Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen.

The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat.

In hypertension, aldosterone has been demonstrated to play a crucial role in cardiac fibrosis, which generally increases cardiac morbidity and death. However, few studies have reported the expression of the mineralocorticoid receptor (MR) and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the heart under hypertensive conditions. Therefore, in this study, spontaneously hypertensive rats (SHR) were examined to elucidate the possible actions of mineralocorticoids via binding to MR.

Expression of androgen receptor and 5alpha-reductase types 1 and 2 in early gestation fetal lung: a possible correlation with branching morphogenesis.

The bioactive and potent androgen 5alpha-dihydrotestosterone (DHT) has been postulated to be involved in the development of branching morphogenesis in the human fetal lung, but its expression has not been examined. We therefore examined the expression of the androgen receptor (AR) and 5alpha-reductases (type 1 and type 2), which catalyse the conversion of testosterone into DHT, in the human fetal lung using immunohistochemistry and reverse transcription-PCR (RT-PCR). Immunoreactive AR was detected predominantly in the nuclei of epithelial cells of the budding component of the early gestational fetal lung.

Orexin-A expression in human peripheral tissues.

Orexin-A is a neuropeptide present in the brain and is known to regulate feeding and sleeping. In this study, we examined the systemic distribution of orexin-A in human tissues. Immunoreactivity for orexin-A was detected in ganglion cells of the thoracic sympathetic trunk, myenteric plexuses and endocrine cells of the gastrointestinal tract, islet cells of the pancreas and syncytiotrophoblasts and decidual cells of the placenta.

Dexamethasone upregulates 11beta-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells.

The actions of natural and synthetic glucocorticoids are in part determined by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). We examined whether carbenoxolone, a potent inhibitor of 11beta-HSD, would potentiate the inhibitory action of dexamethasone on interleukin-8 release from BEAS-2B cells, and whether prolonged treatment with dexamethasone at therapeutic doses would upregulate 11beta-HSD2 in the cells. We found that carbenoxolone increased the potency of dexamethasone almost 10-fold.

Progesterone metabolism in human leukemic monoblast U937 cells.

Progesterone markedly inhibits the functions of human macrophages and T lymphocytes, and acts as an immunosuppressant during pregnancy. It is important to examine progesterone metabolites to understand the overall bioactive properties of this sex steroid. However, progesterone metabolism has not been examined in human immune cells.

Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues.

Estrogens play a key role in various target tissues. Enzymes involved in the biosynthesis and metabolism of these sex steroids also regulate estrogenic actions in these tissues. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1), by steroid sulfatase (STS).

Retinoid receptors in the developing human lung.

Nuclear receptors and their ligands are known to play very important roles in lung development. Among these receptors, retinoid receptors, members of the steroid/thyroid hormone receptor superfamily, are classified into retinoic acid receptor (RAR) isoforms alpha, beta, and gamma and retinoid X receptor (RXR) isoforms alpha, beta, and gamma. In addition, isoforms I and II of the orphan receptor chicken ovalbumin upstream promoter-transcription factor (COUP-TF) have been shown to negatively regulate the activation of retinoid receptors.

Progesterone production and actions in the human central nervous system and neurogenic tumors.

Progesterone has been suggested to be involved in the functions of the nervous system, but it has yet to be examined in humans. Progesterone has also been postulated to be involved in the biological behavior of various human neurogenic tumors via progesterone receptors A and B (PR-A and PR-B). In this study we examined the expression of PR and the enzymes responsible for progesterone biosynthesis (P450scc, 3betahydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) in human brain.

Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors.

Human epithelial ovarian neoplasm is well-known to be sex steroid-related, but the possible biological significance of progesterone actions in these tumors remains controversial. In this study, we examined the differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB, using immunohistochemistry and real-time quantitative RT-PCR in normal and neoplastic ovarian tissues, and in cell lines derived from a normal ovarian surface epithelium and an ovarian epithelial carcinoma in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasms. The median H scores for PR isoforms in normal (n = 8), benign (n = 10), borderline (n = 8) and malignant (n = 24) ovarian tissues were as follows; PRA: 194.

Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart.

Urocortin (Ucn) is a new member of the corticotropin-releasing factor (CRF) neuropeptide family and has positive inotropic actions and protective effects against ischemia in the rat heart. Ucn binds with very high affinity to both CRF receptor type 1 (CRF-R1) and CRF receptor type 2 (CRF-R2). However, to date, endogenous ligand(s) for CRF receptors expressed in the human heart have yet to be elucidated.