Abstract:
:MicroRNAs (miRNA) are negative regulators of gene expression at the posttranscriptional level, which are involved in tumorigenesis. Two miRNAs, miR-15a and miR-16, which are located at chromosome 13q14, have been implicated in cell cycle control and apoptosis, but little information is available about their role in solid tumors. To address this question, we established a protocol to quantify miRNAs from laser capture microdissected tissues. Here, we show that miR-15a/miR-16 are frequently deleted or down-regulated in squamous cell carcinomas and adenocarcinomas of the lung. In these tumors, expression of miR-15a/miR-16 inversely correlates with the expression of cyclin D1. In non-small cell lung cancer (NSCLC) cell lines, cyclins D1, D2, and E1 are directly regulated by physiologic concentrations of miR-15a/miR-16. Consistent with these results, overexpression of these miRNAs induces cell cycle arrest in G(1)-G(0). Interestingly, H2009 cells lacking Rb are resistant to miR-15a/miR-16-induced cell cycle arrest, whereas reintroduction of functional Rb resensitizes these cells to miRNA activity. In contrast, down-regulation of Rb in A549 cells by RNA interference confers resistance to these miRNAs. Thus, cell cycle arrest induced by these miRNAs depends on the expression of Rb, confirming that G(1) cyclins are major targets of miR-15a/miR-16 in NSCLC. Our results indicate that miR-15a/miR-16 are implicated in cell cycle control and likely contribute to the tumorigenesis of NSCLC.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bandi N,Zbinden S,Gugger M,Arnold M,Kocher V,Hasan L,Kappeler A,Brunner T,Vassella Edoi
10.1158/0008-5472.CAN-08-4277subject
Has Abstractpub_date
2009-07-01 00:00:00pages
5553-9issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-4277journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder characterized by a defect in nucleotide excision repair. The human nucleotide excision repair and transcription gene ERCC2 is able to restore survival to normal levels after exposure to UV light in XP complementation group D cells. No enhance...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Breast cancer is the second leading cause of cancer death for women in the United States. Of the different subtypes, estrogen receptor-negative (ER(-)) tumors, which are ErbB2+ or triple-negative, carry a relatively poor prognosis. In this study, we used system-wide analysis of breast cancer proteomes to identify prot...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3711
更新日期:2012-05-01 00:00:00
abstract::The study by Jaratlerdsiri and colleagues represents the first whole-genome sequencing study of prostate cancer from men in sub-Saharan Africa. Preliminary findings include a higher tumor mutation burden in these tumors compared with data from other available prostate cancer cohorts. Although larger studies are needed...
journal_title:Cancer research
pub_type: 评论,杂志文章
doi:10.1158/0008-5472.CAN-18-3382
更新日期:2018-12-15 00:00:00
abstract::Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-15 00:00:00
abstract::Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that ad...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2541
更新日期:2014-01-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course, whereas others having an indolent behavior. We conducted an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B-cell receptors (BcR) ma...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-1615
更新日期:2012-10-15 00:00:00
abstract::Previous cytogenetic analysis has revealed frequent losses of chromosome 1p21-22 in human malignant mesothelioma, suggesting that the loss or inactivation of a tumor suppressor gene's) residing at this site may contribute to the tumorigenic conversion of mesothelial cells. To more precisely define the location of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Liposome formulations of camptothecins have been actively pursued because of the potential for significant pharmacologic advantages from successful drug delivery of this important class of anticancer drugs. We describe nanoliposomal CPT-11, a novel nanoparticle/liposome construct containing CPT-11 (irinotecan) with un...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4007
更新日期:2006-03-15 00:00:00
abstract::The hypothesis that induction of immortalization of rodent cells follows one-hit kinetics was tested by the determination of frequencies of immortalization of Syrian hamster embryo cells after treatment with benzo(a)pyrene, X-rays, or ethylnitrosourea. Contrary to expectation, immortalization did not occur in a single...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-15 00:00:00
abstract::Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)-induced rat tongue lesions and the postinitiation chemopreventive potential of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 344 male rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 1...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-02-15 00:00:00
abstract::Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein. In this study different stages of breast cancer progression wer...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::The class of folate antimetabolites typified by (6R)-dideazatetrahydrofolate (lometrexol, DDATHF) are specific inhibitors of de novo purine synthesis because of potent inhibition of glycinamide ribonucleotide formyltransferase (GART) but do not induce detectable levels of DNA strand breaks. As such, they are a test ca...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-09-15 00:00:00
abstract::Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable polyanhydride matri...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::Methyl methanesulfonate (MMS), a direct-acting alkylating agent, is a strong brain carcinogen but a poor hepatocarcinogen in rats. To elucidate the mechanism(s) leading to tissue-specific carcinogenesis in response to MMS, we compared the activation of the stress-activated protein kinases (SAPKs), the c-Jun NH2-termin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary cancer cells. The CYCLIN D1-TROP2 mRNA was shown to be a potent oncogene as it transforms naïve, primary cells in vitro and induces aggressive tumor growth in vivo in cooperation with activated RAS. Silencing of the chimeric mRNA inhibits the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6135
更新日期:2008-10-01 00:00:00
abstract::The peroxiredoxins (Prx) are conserved antioxidant proteins that use cysteine as the primary site of oxidation during the reduction of peroxides. Many organisms have more than one isoform of Prx. Deletion of TSA1, one of five Prxs in yeast Saccharomyces cerevisiae, results in accumulation of a broad spectrum of mutati...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2683
更新日期:2008-02-15 00:00:00
abstract::Forty patients with relapsed (26) or refractory (14) myeloma were treated with epirubicin of doses of 75, 90, 105, and 120 mg/m2 in groups of 6 or more patients to test for response, maximum tolerated dose, and toxicity. Thirteen patients had received prior doxorubicin and were included in the dose findings part of th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract::Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)) stimulates tumor cell growth and progression. However, the mechanisms by which PGE(2) increases tumor growth remain incompletely understood. In studies performed in non-small cell lung carcinoma (NSCLC) cells, we found that PGE(2) stimulates the expression of integr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2677
更新日期:2009-02-01 00:00:00
abstract::The ability of glucocorticoids (GCs) to induce death in lymphoid-origin cells is the basis for their frequent use in the therapy of various human hematological malignancies. However, the occurrence of primary or secondary GC resistance limits their clinical usefulness. Prior investigations into the mechanism of GC res...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Although ethanol has generally not been found to induce cancer in experimental animals, the consumption of alcoholic beverages has been linked to increased risks of several cancers in humans. Risks of oral, pharyngeal, laryngeal, esophageal, and liver cancer are elevated among drinkers, typically in proportion to the ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1992-04-01 00:00:00
abstract::Administration of 0.75% 2(3)-tert-butyl-4-hydroxyanisole (BHA) in AIN-76A diet to female CD-1 mice for 3 weeks increased liver microsomal glucuronidation of estradiol, estrone, 4-aminophenol, and 4-nitrophenol by 103, 187, 162, and 92%, respectively (at pH 7.4). The overall rate of NADPH-dependent metabolism of estrad...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-06-15 00:00:00
abstract::The G protein-coupled formylpeptide receptor (FPR), which mediates leukocyte migration in response to bacterial and host-derived chemotactic peptides, promotes the chemotaxis, survival, and tumorigenesis of highly malignant human glioblastoma cells. Because glioblastoma cells may also express other receptors for growt...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0691
更新日期:2007-06-15 00:00:00
abstract::We have used high-pressure liquid chromatography and the Salmonella/microsome mutagenicity test to look for mutagenic impurities in 11 carcinogens and noncarcinogens. Because of the million-fold range in mutagenic potency observed in the Salmonella test, even trace amounts of potent mutagenic impurities in a nonmutage...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1966
更新日期:2011-03-01 00:00:00
abstract::Tumor-initiating properties of complete carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA) are well known but not the mechanism of DMBA-mediated tumor promotion. Our hypothesis is that interleukin (IL)-1alpha, an early proinflammatory cytokine that initiates a cascade of other cytokines and growth factors, is u...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-15 00:00:00
abstract::Little is known about the genetic and molecular events leading to the early stages of human astrocytoma formation. To examine this issue, we analyzed the significance of sequential accumulation of two somatic point mutations (R267W and E258D) in the TP53 gene during the initiation of astrocytoma in a patient born with...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-05-15 00:00:00
abstract::Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high con...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1990-10-15 00:00:00
abstract::The mammary carcinoma cell line MFM-223 is characterized by high androgen and low estrogen and progesterone receptor levels. With the dextran charcoal method, androgen binding was determined at 160 fmol/mg protein corresponding to approximately 100,000 binding sites per cell in whole cell binding assays. The estrogen ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Piroxantrone is an anthrapyrazole derivative with broad antitumor activity in vitro. In previous phase I trials, the dose-limiting toxicity of this agent was myelosuppression. Therefore, a phase I and pharmacokinetic study of a 1-h infusion of piroxantrone in combination with granulocyte-colony stimulating factor was ...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1993-06-01 00:00:00