Abstract:
:Pathologic conditions associated with hyperinsulinemia, such as obesity, metabolic syndrome, and diabetes, seem to increase the risk of breast cancer. Here, we studied molecular mechanisms by which insulin activates the expression of leptin, an obesity hormone that has been shown to promote breast cancer progression in an autocrine or paracrine way. Using MDA-MB-231 breast cancer cells, we found that (a) insulin stimulated leptin mRNA and protein expression, which was associated with increased activation of the leptin gene promoter; (b) insulin increased nuclear accumulation of transcription factors hypoxia inducible factor (HIF)-1alpha and Sp1 and their loading on the leptin promoter; (c) small interfering RNA (siRNA)-mediated knockdown of either HIF-1alpha or Sp1 significantly down-regulated insulin-induced leptin mRNA and protein expression; further inhibition of leptin expression was observed under the combined HIF-1alpha and Sp1 siRNA treatment; (d) inhibition of extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol-3-OH kinase (PI-3K) pathways significantly, albeit partially, decreased insulin-dependent leptin mRNA and protein expression, which coincided with reduced association of HIF-1alpha and/or Sp1 with specific leptin promoter regions; and (e) inhibition of ERK1/2 reduced recruitment of both HIF-1alpha and Sp1 to the leptin promoter, whereas down-regulation of PI-3K influenced only HIF-1alpha binding. In summary, our data suggest that hyperinsulinemia could induce breast cancer progression through leptin-dependent mechanisms. In MDA-MB-231 cells, this process requires Sp1- and HIF-1alpha-mediated leptin gene transcription and is partially regulated by the PI-3K and ERK1/2 pathways.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bartella V,Cascio S,Fiorio E,Auriemma A,Russo A,Surmacz Edoi
10.1158/0008-5472.CAN-08-0642subject
Has Abstractpub_date
2008-06-15 00:00:00pages
4919-27issue
12eissn
0008-5472issn
1538-7445pii
68/12/4919journal_volume
68pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The POU-domain transcription factor Oct-1 is widely expressed in adult tissues and has been proposed to regulate a large group of target genes. Microarray expression profiling was used to evaluate gene expression changes in Oct-1-deficient mouse fibroblasts. A number of genes associated with cellular stress exhibited ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2399
更新日期:2005-12-01 00:00:00
abstract::Partially purified preparations of mouse interferon, administered during the 2-day period following the administration of a toxic dose of 5-fluorouracil (FUra), yielded significant protection from mortality in BALB/c X DBA/2 F1 mice. Protection against FUra-induced toxicity was also observed when the interferon induce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib),...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2138
更新日期:2016-03-01 00:00:00
abstract::Farnesol (FOH) and other isoprenoid alcohols induce apoptosis in various carcinoma cells and inhibit tumorigenesis in several in vivo models. However, the mechanisms by which they mediate their effects are not yet fully understood. In this study, we show that FOH is an effective inducer of apoptosis in several lung ca...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0931
更新日期:2007-08-15 00:00:00
abstract::The association of intrauterine exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities in young women has been well documented. Although the incidence of vaginal adenocarcinoma was low in the exposed population, vaginal adenosis, a nonmalignant abnormality, was quite co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hC...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-07-15 00:00:00
abstract::It is well known that normal human diploid fibroblasts undergo a significant, p53-dependent arrest in the G1 phase of the cell cycle after exposure to ionizing radiation. The presence and magnitude of a G1 arrest in human tumor cell lines, however, has been controversial, particularly in cells derived from solid tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4608
更新日期:2007-05-15 00:00:00
abstract::The clinical utility of cisplatin to treat human malignancies is often limited by the development of drug resistance. We have previously shown that cisplatin-resistant human KB adenocarcinoma cells that are cross-resistant to methotrexate and heavy metals have altered endocytic recycling. In this work, we tracked lipi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3436
更新日期:2006-02-15 00:00:00
abstract::Human cutaneous fatty acid-binding protein (C-FABP) gene is capable of inducing the metastatic phenotype when overexpressed in nonmetastatic rat Rama 37 cells. However, the mechanism of how it induces metastasis is not clear. Northern and slot blot analyses revealed that expression of the endogenous vascular endotheli...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::As a specific competitive inhibitor of 5alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone, finasteride is being extensively used for the treatment of benign prostatic hyperplasia and in experimental settings for prostate cancer. In this study, we showed that finasteride markedl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-02-15 00:00:00
abstract::Virion antigens of feline leukemia virus are associated with HLA antigens in the membrane of human cells infected with the virus. Feline leukemia virus produced by these cells incorporates host membrane antigens into the virion envelope, making the virus susceptible to lysis by antisera directed to HLA or to uninfecte...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::A slight induction of granulocytic differentiation of HL-60 cells occurred after treatment with antileukemia chemotherapeutic agents Adriamycin (ADM) and daunomycin (DM). Addition of an inhibitor (sphinganine, SP) of protein kinase C (PKC) enhanced 2-4-fold the ADM or DM-induced differentiation. This phenomenon was ac...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Variant cell lines that are sensitive to density-dependent inhibition of growth have been isolated from three of four SV40-transformed human fibroblast cell lines. Variants were isolated by plating the transformed cells at low density, by treating them with 5-fluorodeoxyuridine, or by growing them on glutaraldehyde-fi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Two subclones of L1210 murine leukemia (L1210-46.1 and L1210-56.3) were isolated in the absence of selective agents. Subclone 56.3 appeared to be more sensitive than was subclone 46.1 to treatment with dexamethasone, 1-beta-D-arabinofuranosyl cytosine, vincristine, and X-irradiation. No differences between the parent ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-06-01 00:00:00
abstract::A comprehensive description of genomic alterations in lung squamous cell carcinoma (lung SCC) has recently been reported, enabling the identification of genomic events that contribute to the oncogenesis of this disease. In lung SCC, one of the most frequently altered receptor tyrosine kinase families is the fibroblast...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-3950
更新日期:2013-08-15 00:00:00
abstract::Isoprenoid inhibitors are being evaluated as agents for the treatment of cancer. Their antitumor activity is attributed to inhibition of post-translational modification of Ras, which is crucial for its translocation and attachment to the plasma membrane, and ultimate involvement in signal transduction. However, whethe...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3416
更新日期:2006-01-15 00:00:00
abstract::Plasma levels of luteinizing hormone, sex hormone binding globulin, and antithrombin III were measured in pre- and postmenopausal breast cancer patients receiving adjuvant combination chemotherapy or combination chemotherapy and long-term tamoxifen therapy. The aim was to determine the estrogen-like effects of tamoxif...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-08-15 00:00:00
abstract::Repurposing "old" drugs can facilitate rapid clinical translation but necessitates novel mechanistic insight. Warfarin, a vitamin K "antagonist" used clinically for the prevention of thrombosis for more than 50 years, has been shown to have anticancer effects. We hypothesized that the molecular mechanism underlying it...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-2887-T
更新日期:2015-09-15 00:00:00
abstract::Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5460
更新日期:2008-04-15 00:00:00
abstract::The tumor microenvironment is characterized by regions of fluctuating and chronic hypoxia, low pH, and nutrient deprivation. It has been proposed that this unique tissue environment itself may constitute a major cause of the genetic instability seen in cancer. To investigate possible mechanisms by which the tumor micr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::The present study with N-methyl-N-nitrosourea and rat brain DNA was performed in order to study the distribution of alkylated products and the difference in the removal of these products from DNase I-sensitive and -resistant regions of DNA. Nuclei were isolated from N-[3H]methyl-N-nitrosourea-treated rats and incubate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::In previous studies, we have demonstrated that transferrin-gallium inhibits cellular proliferation by a mechanism whereby cellular iron utilization is impaired. Since indium, a similar class 3A metal, has not been well studied, we examined its effects on cellular iron uptake and cellular proliferation. In these studie...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Mutations of the tumor suppressor E-cadherin and overexpression of the receptor tyrosine kinase epidermal growth factor receptor (EGFR) are among the most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between E-cadherin and EGFR th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1588
更新日期:2008-02-01 00:00:00
abstract::MCF-7 cells have been shown to contain estrogen receptor in several cell fractions following homogenization: nuclei, microsomes, and cytosol. The amount of 17 beta-estradiol-binding capacity found in each cellular compartment depended on the inclusion of detergent in homogenization buffers and on the use of 0.25 M suc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::The XC infectious center assay was used to study the nature of the lymphoid cells producing N-tropic C-type viruses in preleukemic AKR mice. Viral production by thymic cell suspensions was very low and was possibly due to contaminating cells. Production at least 100-fold higher was found in spleen cells and was probab...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
abstract::Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here, we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-2942
更新日期:2017-05-01 00:00:00
abstract::Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1636
更新日期:2007-11-01 00:00:00
abstract::CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and activated type II pneumocytes. We have examined the expression of CD44 in 12 human l...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::We studied the effects of interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) on MCF-7 breast cancer cells to determine whether these cytokines act additively/synergistically to alter cell growth and metabolism. We found that IL-1 alone (1000 units/ml) inhibited cell growth to a greater degree (83.8%) than IL-6 alone ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00