Abstract:
:Growth factor receptors of the tyrosine kinase family regulate proliferation of a variety of cell types. In some human cancers, the epidermal growth factor receptor (EGFR) and its ligands often are overexpressed, leading to both constitutive and autocrine activation. Intracellular signaling via this receptor takes place through several mechanisms of action, including activation of ras and the mitogen-activated protein kinase (MAPK) pathway. Our previous studies have shown that human squamous cell carcinoma (SCC) lines overexpress EGFR and do not increase proliferation in response to exogenous epidermal growth factor (EGF). The vitamin A metabolite retinoic acid (RA) has been used as a chemotherapeutic drug in the treatment of SCC. RA decreases proliferation of SCC lines, in part owing to inhibition of EGFR expression. However, we previously found that treatment of SCC lines with inhibitory doses of RA sensitized cells to the proliferative effects of EGF. We now present a mechanism of action for this effect. RA inhibited expression of EGFR and proteins in the MAPK signaling pathway. Expression of these molecules returned to basal levels within 24 h after RA withdrawal. RA also inhibited autocrine secretion of EGF, which returned to basal levels with slower kinetics. During this time, addition of exogenous EGF stimulated mitosis in SCC lines. These data suggested that signaling proteins downstream of overexpressed EGFR may have limited the mitotic response in SCC lines. In support of this hypothesis, overexpression of the EGFR adaptor protein Grb2 increased cell proliferation and restored EGF-induced mitosis.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Crowe DL,Tsang KJdoi
10.1002/mc.10011subject
Has Abstractpub_date
2001-12-01 00:00:00pages
187-94issue
4eissn
0899-1987issn
1098-2744pii
10.1002/mc.10011journal_volume
32pub_type
杂志文章abstract::Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c-MET has been shown to be deregulated in many cancers, but the role of c-MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression a...
journal_title:Molecular carcinogenesis
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更新日期:2016-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that CpG methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadheri...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10064
更新日期:2002-08-01 00:00:00
abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22023
更新日期:2014-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20393
更新日期:2008-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2015-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22268
更新日期:2016-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20513
更新日期:2009-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20090
更新日期:2005-12-01 00:00:00
abstract::We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090105
更新日期:1994-01-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E-box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Rece...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22994
更新日期:2019-06-01 00:00:00
abstract::Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were de...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940140411
更新日期:1995-12-01 00:00:00
abstract::LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3β/...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22321
更新日期:2016-05-01 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony for...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23199
更新日期:2020-06-01 00:00:00
abstract::microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt pathway is commonly altered in glioblastoma. Glioblastoma has not been previously evaluated for miR-577 expression. Glioblastoma tumors and cell lines were evaluat...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22304
更新日期:2016-05-01 00:00:00
abstract::Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracel...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22033
更新日期:2014-10-01 00:00:00
abstract::Paclitaxel is the last choice for the treatment of advanced melanoma as a second-line chemotherapeutic agent, but there are still many cases of intrinsic resistance to paclitaxel in melanoma and the reasons that cause paclitaxel resistance remain unclear. Here, we identified that high expression of SRY-box transcripti...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23148
更新日期:2020-03-01 00:00:00
abstract::The Ki-ras proto-oncogene is activated by specific point mutations and is the transforming gene often identified in rodent and human lung tumors. An in vitro model to aid in the study of the consequences of Ki-ras activation and expression in mouse lung is needed. Accordingly, we have examined cell lines derived from ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030508
更新日期:1990-01-01 00:00:00
abstract::Male F(1) hybrids between MSM mice carrying a deficient p53 allele and BALB/c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtained, 46 of which developed in mice carrying the deficient p53 allele. Because the Y chromosome contributes little to cellular function, the stability of the Y chromosome...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050412
更新日期:1992-01-01 00:00:00
abstract::The influence of the tumor promoter 2-acetylaminofluorene (2-AAF) on cell proliferation and on the epidermal growth factor receptor (EGFR) system was assessed in normal and nodular rat livers. DNA replication in vivo was inhibited below the detection level after 8d of dietary 2-AAF treatment of previously unexposed ra...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100207
更新日期:1994-06-01 00:00:00
abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20664
更新日期:2010-10-01 00:00:00
abstract::C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas st...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22623
更新日期:2017-06-01 00:00:00
abstract::Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well-k...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.23183
更新日期:2020-07-01 00:00:00
abstract::Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22912
更新日期:2019-01-01 00:00:00
abstract::Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21976
更新日期:2014-02-01 00:00:00
abstract::The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacc...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
abstract::Transformation of cloned rat embryo fibroblast (CREF) cells with the wild-type 5 adenovirus (wtAd5) transforming genes E1A and E1B (which extend from 0 to 11.2 map units) results in morphologically transformed cells that exhibit an increased saturation density in monolayer culture and display an anchorage-independent ...
journal_title:Molecular carcinogenesis
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doi:10.1002/mc.2940050207
更新日期:1992-01-01 00:00:00