Expression of EGFR Family and Steroid Hormone Receptors in Ductal Carcinoma in situ of the Breast

The expression of EGFR family and steroid hormone receptors was examined in a series of 40 cases of pure ductal carcinoma in situ (DCIS) of the breast by immunohistochemical staining of paraffin-embedded sections. Hematoxylin and eosin-stained sections were used to classify the tumors according to the published criteria by Holland et al. (Holland R, Peterse JL, Millis RR, et al. Semin Diagn Pathol. 1994;11:167-180). Of the tumors 48% were immunoreactive for EGFR, 63% for c-erbB-2, 78% for c-erbB-3, 95% for c-erbB-4, 88%for estrogen receptor (ER) and 80% for progesterone receptor (PR). Statistically significant association between histological grade (differentiation) and c-erbB-2 protein expression was seen ( p <.001). In addition, expression of c-erbB-4 protein was associated with c-erbB-2 ( p =.004), c-erbB-3 ( p =.058), ER ( p =.002) and PR ( p =.004). It is concluded that c-erbB-2 expression in DCIS is associated with high-grade pathological features, and a higher c-erbB-2 expression is seen in DCIS than in invasive breast carcinomas. A possible association between extensive expression of c-erbB-4 and steroid hormone receptors in proliferative and premalignant breast epithelial cells and the c-erbB-2 expression in DCIS and invasive breast carcinomas is discussed.     

The Effects of Sex Protein Receptors and Sex Steroid Hormone Gene Polymorphisms on Breast Cancer Risk

Breast cancer is a common disease and a major cause of death among women throughout the world. Various genes are believed to be involved in the initiation and progression of the disease. Some polymorphisms of these genes increase susceptibility to breast cancer in particular ethnicities. This study used electronic literature search to review the effects of different sex steroid hormone gene polymorphisms on breast cancer risk. Our findings indicated that some polymorphisms in estrogen receptor alpha (ER-α), ER-β, progesterone receptor (PGR), pregnane X receptor (PXR), and cytochrome P450 enzymes (CYPs) affected breast cancer susceptibility, especially in African American women.     

卵巢宫内膜异位症组织的性激素受体及血清激素水平的测定

对40例非病性卵巢和19例卵巢宫内膜异位症组织进行胞浆、胞核ER、PR、AR水平及外周血F5H、LH、E2、P、T水平的测定.结果显示:两组的ERn、PRn、ARn均显著高于ERc、PRc、ARc,两组的ERn与ER、PRn与PR比较,非病性卵巢组差异有显著性,卵巢宫内膜异位症组差异无显著性,说明非病性卵巢组的ERc与ERn、PRc与PRn之间存在一定的比例关系,而卵巢宫内异位症组其比例关系失调;卵巢宫内膜异位症组ERc显著低于非病性卵巢组,P与ERc、ER呈显著负相关,ERc与PRc呈显著正相关,说明卵巢宫内膜异位症组织与宫腔内膜的性质相同,都受性激素的相同调节.     

乳腺单纯癌细胞形态定量及临床病理特征与预后的关系

分析33例乳腺单纯癌细胞形态定量、临床病理特征及性激素受体(SR)表达与术后5年生存率的关系。结果显示:(1)癌细胞核大(包括平均核直径、周长、面积)、异型性明显、形状因子小、核分裂象多见者预后差;(2)组织学Ⅰ-Ⅱ级、SR表达水平高、无淋巴结转移者及高龄患者预后较好;(3)少数单纯癌虽然细胞核小,但若细胞分化较差、缺乏SR表达且伴有淋巴转移者仍预后不良。表明综合考虑单纯癌细胞和组织病理学特征、SR状态及临床特点,才能更好地估计预后。     

Evidence of Steroid Receptors in Human Osteoblast-Like Cells

A nuclear binding assay was used to demonstrate steroid receptors in normal human osteoblast-like cells. Nuclear binding of [³H] estradiol was found in 27 of 30 (90%) cell strains and nuclear binding of [³H] androgen was identified in 21 of 25 (84%) separate osteoblast cell strains. The nuclear binding was saturable and steroid-specific. Estrogen and androgen receptor gene expression was confirmed by RNA blot analysis. These data suggest that circulating sex steroids may act directly on normal human osteoblasts through receptor-mediated mechanisms.     

Proliferative Activity and Level of Steroid Hormone Receptors in the Myometrium and Myoma Nodes in Different Phases of Menstrual Cycle

We compared proliferative activity and levels of steroid receptors in the myometrium and myoma nodes in patients with uterine myoma in different phases of menstrual cycle. Maximum proliferative activity was observed at the periphery of myoma nodes in the the secretory phase of the cycle. The content of progesterone receptors at the periphery and in the center of myoma nodes was lower in the proliferative phase of the cycle than in the secretory phase. Steroid regulation of proliferative activity in the myoma nodes in the the secretory phase through modulation of the content of progesterone receptors is hypothesized.     

乳腺癌及癌前病变细胞DNA的定量分析及其与激素受体、癌胚抗原的关系

检测119例乳腺癌及40例癌旁增生性病变的DNA含量、类固醇激素受体(SR)和癌胚抗原(CEA)表达。结果显示:正常导管上皮、不同级别的癌旁增生上皮和癌细胞的DNA含量均有明显差异。多倍体的出现是细胞恶变的早期表现。癌细胞DNA含量与SR水平呈负相关,而与CEA表达呈正相关。SR阳性乳癌患者术后存活5年以上者DNA含量和核面积均小于5年内死亡者。     

慢性肾炎性激素受体改变及意义

应用放射配体结合分析检测48例慢性肾炎外周血白细胞雄激素受体（AR）及雌激素受体（ER）的结合容量。男性、育龄女性及绝经女性三组患者白细胞ER及ER／AR比值明显升高。提示性激素受体的改变与慢性肾炎的发病有一定关联。     

p53 Overexpression and Steroid Hormone Receptor Status in Endometrial Carcinoma

Mutations of the p53 tumor suppressor gene often occur in a variety of human malignant tumors and are frequently associated with overexpression of p53 protein. This study was designed to examine indirectly the frequency of p53 protein in primary endometrial carcinoma and to correlate the overexpression with steroid hormone receptor status including pS2 protein status. The study was performed on 79 formalin-fixed, paraffin-embedded tissues of endometrial carcinoma. P53 protein overexpression was detected by means of immunohistochemistry using monoclonal antibody NCL-p53-DO7. Estrogen and progesterone receptor status was determined by immunohistochemistry using the monoclonal antibodies NCL-ER-LH(2) and NCL-PGR, respectively, and the pS2 protein using polyclonal antibody NCL-pS2. Overexpression of p53 protein was found in 27 (34%) of the 79 endometrial carcinomas. A strong positive relationship was demonstrated between histologic grade and p53 protein overexpression. There was a significant correlation between p53 protein overexpression and negative estrogen receptor status (49%) negative progesterone receptor status (49%) as well as a negative pS2 protein (45%). The results suggest that overexpression of p53 is associated with high malignant potential. However, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial carcinomas. Int J Surg Pathol 8(3):213-222, 2000     

桥本甲状腺炎患者外周血白细胞性激素受体的改变及其意义

应用放射配体结合法检测３８例则性淋巴细胞性甲状腺炎（桥本甲状腺炎）患者外周血白细胞雄性激素受体（ＡＲ）及雌激素受体（ＥＲ）。同时用方向免疫分析检测血浆黄体生成素（ＬＨ）、卵泡刺激素（ＦＳＨ）、睾酮（Ｔ）、雌二醇（Ｅ２）及Ｔ３、Ｔ４和ＴＳＨ。结果表明桥末甲状腺炎患者ＬＨ、ＦＳＨ、Ｅ２和Ｔ无明显改变；白细胞ＥＲ明显升高，ＡＲ无明显改变；ＥＲ／ＡＲ比值明显升高。以上结果提示ＥＲ及ＥＲ／ＡＲ比值的升高与桥     

Steroid Hormone Action in Musculoskeletal Cells Involves Membrane Receptor and Nuclear Receptor Mechanisms

Steroid hormones regulate target cells through traditional nuclear mechanisms as well as by membrane mechanisms. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 bind membrane receptors (mVDR) and mediate their effects on the physiological responses of musculoskeletal cells via protein kinase C (PKC). In cultures of costochondral growth plate chondrocytes, 1 &#102 ,25(OH) 2 D 3 binds the 1,25-mVDR in growth zone cells, activating phospholipase C (PLC), leading to diacylglycerol (DAG) production and PKC translocation to the plasma membrane. It also activates PLA 2 , increasing arachidonic acid release and prostaglandin synthesis. 24R,25(OH) 2 D 3 binds its membrane receptor in resting zone chondrocytes, activating phospholipase D (PLD), and increasing DAG and PKC activity, but translocation does not occur. PLA 2 activity is decreased, reducing arachidonic acid and prostaglandin production. 17 &#103 -Estradiol (E 2 ) activates PKC in both cartilage cells, but DAG is not involved. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 also increase PKC in osteoblasts in a cell-specific manner. Antibodies to the 1,25-mVDR block PKC activation. Membrane-mediated events influence gene expression via signaling cascades, including the ERK1/2 MAP kinases. The ability of steroid hormones to initiate events nongenomically is important for regulation of matrix vesicle (MV) function in the extracellular matrix. MVs have mVDRs, but ligand binding inhibits PKC-zeta (PKC &#145 ) via a mechanism that differs from PKC &#102 activation in the plasma membranes. Treatment of MVs from growth zone chondrocyte cultures with 1 &#102 ,25(OH) 2 D 3 releases stromelysin-1 (MMP-3) and increases TGF- &#103 activation. MMP-3 is also involved in proteoglycan degradation, facilitating calcification. 24R,25(OH) 2 D 3 inhibits PKC &#145 in MV from resting zone cell cultures and inhibits MMP-3 release. Chondrocytes and osteoblasts produce 1,25(OH) 2 D 3 , 24,25(OH) 2 D 3 , and E 2 ; thus, locally produced steroids may function as autocrine regulators of matrix events, including matrix vesicle enzyme activity and matrix protein remodelling during longitudinal growth, calcification, and growth factor activation.     

C. elegans DAF-12, Nuclear Hormone Receptors and human longevity and disease at old age

In Caenorhabditis elegans, DAF-12 appears to be a decisive checkpoint for many life history traits including longevity. The daf-12 gene encodes a Nuclear Hormone Receptor (NHR) and is member of a superfamily that is abundantly represented throughout the animal kingdom, including humans. It is, however, unclear which of the human receptor representatives are most similar to DAF-12, and what their role is in determining human longevity and disease at old age. Using a sequence similarity search, we identified human NHRs similar to C. elegans DAF-12 and found that, based on sequence similarity, Liver X Receptor A and B are most similar to C. elegans DAF-12, followed by the Pregnane X Receptor, Vitamin D Receptor, Constitutive Andosteron Receptor and the Farnesoid X Receptor. Their biological functions include, amongst others, detoxification and immunomodulation. Both are processes that are involved in protecting the body from harmful environmental influences. Furthermore, the DAF-12 signalling systems seem to be functionally conserved and all six human NHRs have cholesterol derived compounds as their ligands. We conclude that the DAF-12 signalling system seems to be evolutionary conserved and that NHRs in man are critical for body homeostasis and survival. Genomic variations in these NHRs or their target genes are prime candidates for the regulation of human lifespan and disease at old age.     

Bi-directional Signaling between Gastrointestinal Peptide Hormone Receptors and Epidermal Growth Factor Receptor

The mechanisms mediating the proliferative effects of gastrointestinal (GI) peptide hormones and their cognate G protein-coupled receptors are associated intimately with epidermal growth factor (EGF) receptor-regulated signaling pathways. Although transactivation of the EGF receptor is now recognized as a critical component in GI peptide hormone regulation of mitogenic signaling and cell migration, their interactions are far more complex and include potentiation of intracellular signaling pathways, regulation of ligand expression and release, and modulation of cell surface receptor expression. Mitogen-activated protein kinases play a central role integrating the signals from these receptor systems. This review summarizes the mechanisms that intertwine GI peptide hormone receptor- and EGF receptor-activation and functions.