Abstract:
PURPOSE:G-protein-coupled receptors are known to mediate cell growth via divergent signaling pathways. It has been reported that colon cancer cells express muscarinic acetylcholine receptor (mAChR) although their functional role is largely unknown. The aim of this study is to elucidate possible mechanisms responsible for the growth-promoting effect of mAChRs in colon cancer cells by using colon cancer cell line T84. METHODS:Carbachol, a stable mAChR agonist, dose-dependently induced cell growth with a maximal effect observed at 100 microM, equipotent with 1 nM EGF. 4-DAMP, a specific antagonist of subtype 3 mAChR, inhibited the stimulatory effect by carbachol, suggesting that the growth-promoting effect was receptor-mediated. Carbachol also dose-dependently stimulated extracellular signal-regulated protein kinase (ERK) activation. This effect was inhibited by PD98059, an inhibitor of extracellular signal-regulated protein kinase kinase, which also blocked carbachol activation of cell proliferation, indicating that the p21Ras-ERK pathway is an important signaling cascade in the mitogenic effect. To investigate how mAChR activated the p21Ras-ERK pathway, transactivation of epidermal growth factor receptor (EGFR) was examined. RESULTS:Carbachol induced tyrosine phosphorylation of EGFR, which was abolished by an EGFR tyrosine kinase inhibitor AG1478. Transactivation by carbachol was also abrogated by a metalloproteinases (MMPs) inhibitor GM6001 or an EGFR-blocking antibody (LA-1), suggesting that binding of EGFR ligand(s) produced by MMPs may initiate transactivation in a manner dependent on EGFR tyrosine kinase. The tyrosine-phosphorylated EGFR was immunoprecipitated together with GRB2 and tyrosine-phosphorylated Shc, indicating that transactivated EGFR is able to generate downstream signals. AG 1478 and LA-1 inhibited carbachol stimulation of cell growth. CONCLUSIONS:Taken together, our results indicate that the growth-promoting effect of subtype 3 mAChR in colon cancer cells may depend on transactivated EGFR-ERK pathways. EGFR not only receives external stimuli but also serves as a scaffold for downstream signaling molecules.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Ukegawa JI,Takeuchi Y,Kusayanagi S,Mitamura Kdoi
10.1007/s00432-003-0433-ysubject
Has Abstractpub_date
2003-05-01 00:00:00pages
272-8issue
5eissn
0171-5216issn
1432-1335journal_volume
129pub_type
杂志文章abstract:PURPOSE:Tumor angiogenesis is an important factor for the continuous growth of human malignancies and can be used to predict the prognosis for patients. In the current study, we examined the expression of EGF-like domain 7 (EGFL7), an endothelial cell-derived secreted factor, in malignant gliomas and explored its clini...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-010-0832-9
更新日期:2010-11-01 00:00:00
abstract::A continuous line of human breast carcinoma cells, VHB-1, was established in culture following collagenase treatment of an infiltrating duct cell carcinoma. The cells displayed an epithelial pattern and multiplied rapidly. Maintained in monolayer culture, the VHB-1 cells exhibited a 30-h doubling time and a plating ef...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00390864
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abstract::To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gas...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01218524
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abstract:PURPOSE:To investigate the genomic alterations in larynx carcinomas (LaCa) tissues and its prognostics values in predicting survival. METHODS:To analyse the aberrations in the genome of LaCa patients, we used array comparative genomic hybridization in 19 human laryngeal tumour samples. DNA samples were also subjected ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0735-9
更新日期:2010-06-01 00:00:00
abstract:PURPOSE:Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS:This review mainly ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-017-2457-8
更新日期:2017-08-01 00:00:00
abstract:PURPOSE:To investigate the expression of sex steroid receptors in gastric cancer and to correlate their tumor expression profile with the clinicopathological parameters and overall survival of the patients. METHODS:Immunohistochemical methodology was employed in formalin-fixed paraffin-embedded sections from 86 patien...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0531-x
更新日期:2004-05-01 00:00:00
abstract::According to a "two-hit" model, dominantly inherited predisposition to cancer entails a germline mutation, while tumorigenesis requires a second, somatic, mutation. Non-hereditary cancer of the same type requires the same two hits, but both are somatic. The original tumor used in this model, retinoblastoma, involves m...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/BF01366952
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:This study was to investigate whether the topoisomerase (Top) I inhibitor topotecan and the Top II inhibitor etoposide could modulate the hypoxia-induced HIF-1alpha expression in non-small cell lung cancer (NSCLC) cell lines. METHODS:Hypoxic conditions were maintained in a humidified airtight anaerobic incubat...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0543-2
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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更新日期:1983-01-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章
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abstract::Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer pa...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01212719
更新日期:1993-01-01 00:00:00
abstract::A cohort of 5,477 male Japanese physicians was studied to examine the relationship between smoking habits and mortalities from cancer, coronary heart disease (CHD) and stroke over 12.7 years. The logistic regression analysis based on proportional hazard models was used for statistical assessment. The risks of both lun...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00402732
更新日期:1985-01-01 00:00:00
abstract::P-glycoprotein (P-gp), a cell membrane protein, has been found in multidrug-resistant cancer cells. A total of 104 smears from patients with breast-cancer-associated pleural effusions and ovarian-cancer-related peritoneal effusions were studied for P-gp with the antibody C-219 and the avidin-biotin-immunoperoxidase me...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01613000
更新日期:1990-01-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-012-1207-1
更新日期:2012-08-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-007-0333-7
更新日期:2008-06-01 00:00:00
abstract:PURPOSE:Little data exist on characteristics, treatment, and outcome of patients with bone metastases from germ cell cancer. METHODS:A total of 434 patients with poor prognosis germ cell cancer, who underwent primary high-dose chemotherapy (HD-CTX) within two phase II trials, were retrospectively analyzed. RESULTS:40...
journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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doi:10.1007/s00432-003-0519-6
更新日期:2004-03-01 00:00:00
abstract::A dose-response study was carried out in male F344 rats with a specific urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which was administered as a solution in drinking water for up to 112 weeks. BBN was given in four different concentrations, 50, 10, 5, and 1 ppm, to groups of 30 rats. The hi...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00390992
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-008-0388-0
更新日期:2008-10-01 00:00:00
abstract::A total of 30 inbred Wistar rats were orally administered 70 microgram/ml solution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 35 weeks and then tap water for the following 20 to 30 weeks. Four of the 20 females and two of ten males developed carcinoids in the glandular stomach, but no metastasis could be found...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00405896
更新日期:1981-01-01 00:00:00
abstract::A prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the impact of granulocyte/macrophage-colony-stimulating factor (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodysplastic syndromes (MD...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s004320050288
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Triple negative breast cancer (TNBC) harbors a heterogeneous group of carcinomas with poor prognosis and high genetic variability. As a potential aim for targeted therapy, genetic mutations leading to an activation of the phosphoinositide 3-kinase pathway in a catalytic subunit (PIK3CA) in breast cancer have...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
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更新日期:2019-08-01 00:00:00
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journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-005-0062-8
更新日期:2006-06-01 00:00:00
abstract::The epoxide hydratase inhibitor, 1,1,1-trichloro-2,3-propene oxide (TCPO) in combination with benzo[a]pyrene (B[a]P) was injected s.c. in ddN mice. The formation of fibrosarcoma by B[a]P was slightly accelerated at low dose of TCPO, and remarkably inhibited at high dose of TCPO. The correlation of carcinogenesis with ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00413182
更新日期:1980-01-01 00:00:00
abstract::This special report discusses problems relevant to histological diagnosis of cancer after chemo- and/or radiotherapy. One of the issues relates to pitfalls, i.e. over-, under- or misdiagnosis or oversight, stemming from a lack of concern or awareness of therapeutic effects on tumors or normal tissues. Another set of q...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050269
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:To evaluate prognostic factors in estrogen receptor (ER)-positive, operable breast cancer focusing on the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). PATIENTS AND METHODS:A total of 819 patients with ER-positive, operable breast cancer were enrolled. All patients received up...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-011-0976-2
更新日期:2011-07-01 00:00:00