Track topics on Twitter Track topics that are important to you
Breast cancer (BC) is the primary cause of cancer-related mortality among women. Patients who express the estrogen receptor (ER), which mediates the tumorigenic effects of estrogens, respond to antihormonal therapy. Loss of ER expression or acquired resistance to E2 is associated with aggressive malignant phenotypes, which lead to relapse. These BC subtypes overexpress syndecan-1 (SDC1), a transmembrane heparan sulfate proteoglycan that mediates angiogenesis as well as the proliferation and invasiveness of cancer cells. We showed here that the activation of ER-alpha (ERα) by estrogens induces downregulation of SDC1 expression in ER(+) MCF7 cells but not in T47D cells. Loss of ERα expression, induced by RNA interference or a selective ER down-regulator, led to subsequent SDC1 overexpression. E2-dependent downregulation of SDC1 expression required de novo protein synthesis and was antagonized by treatment with BAY 11-7085, an irreversible inhibitor of IκBα phosphorylation, which inhibits the activation of NFκB. Downregulation of SDC1 expression required ERα and activation of IKK, but was independent to downstream transcriptional regulators of NFκB. BAY 11-7085 prevented E2-mediated phosphorylation of ERα on Ser118, increasing its proteasomal degradation, suggesting that IKK stabilized E2-activated ERα, leading to subsequent downregulation of SDC1 expression. Our results showed that sustained ER signaling inhibits SDC1 expression. Such antagonism elucidates the inverse correlation between SDC1 and ER expression in ER(+) BC as well as the overexpression of SDC1 in hormone receptor-negative BC subtypes with the most aggressive phenotypes. These results identify SDC1 as an attractive therapeutic target for BC as well as for other endocrine-associated cancers.
This article was published in the following journal.
Name: Endocrine-related cancer
Syndecan-1 is heparan sulfate proteoglycans (HSPGs) that is used as coreceptors for signaling of growth factors. The comprehensive effect of syndecan-1 is to augment receptor stimulation at little lig...
Expression of estrogen receptor α in breast cancer is essential for estrogen-dependent growth and partially determines the breast cancer subtype. In premenopausal women, expression of estrogen-regula...
Ductal carcinoma in situ (DCIS) represents a heterogeneous disease in its histologic appearance and biological potential. Some women treated for DCIS subsequently develop invasive breast cancer. DCIS ...
The aim of this study was to evaluate the reliability of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) expression levels in Cellprep® (CP).
According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estr...
Basal like breast carcinoma is a Her2, estrogen receptor (ER) progesterone receptor (PR) negative breast cancer. It is notable for the high level of epidermal growth factor receptor (EGFR)...
The purpose of this study is to assess clinical outcomes after Letrozole treatment according to the estrogen receptor expression in postmenopausal women with hormone receptor positive brea...
This randomized clinical trial studies tamoxifen citrate in treating premenopausal women with estrogen receptor (ER)-positive breast cancer. Estrogen can cause the growth of breast cancer ...
AR is a steroid hormone receptor that regulates various genes' expression and affects cellular proliferation and differentiation. Androgens interact with AR, exert their paracrine action o...
This trial studies how well 68Ga-RM2 works with PET/MRI in imaging patients with estrogen receptor-positive breast cancer. 68Ga-RM2 is an agent used in diagnostic imaging. A PET/MRI scan m...
One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.
A condition in which abnormal cells have not spread outside the duct, lobule, or nipple to other tissues of the breast. There are 3 types of breast carcinoma in situ: DUCTAL CARCINOMA IN SITU; LOBULAR CARCINOMA IN SITU; and PAGET DISEASE OF THE NIPPLE
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.
Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.
A secretoglobin that is produced by the MAMMARY GLAND of HUMANS and may be involved in the binding of ANDROGENS and other STEROIDS. The expression of this protein in normal breast epithelium and in human breast cancer has made it an important histological marker.
Track and monitor developments in breast cancer research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...