Clinical implications of expression of ETS-1 related to angiogenesis in uterine cervical cancers

Fujimoto, Jiro; Aoki, Ikumi; Toyoki, Hiroshi; Khatun, Sufia; Tamaya, Teruhiko

doi:10.1093/annonc/mdf248

Cited by 53 publications

(45 citation statements)

References 25 publications

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“…28,29) These findings prompted us to study whether the proto-oncogene ets-1 acts as an angiogenic mediator in ovarian cancers.…”

Section: )mentioning

confidence: 99%

“…28,29) Deoxynucleic acid construction of the internal standard was done by PCR from a BamHI/ EcoRI-ligated fragment of V-erbB (Clontech Laboratories, Palo Alto, CA) with two sets of oligonucleotide primer sequences. The sequences of the first set of primers for ets-1 mRNA (MIMIC ets-1-5′ and MIMIC ets-1-3′) in the first PCR were as follows: MIMIC ets-1-5′, 5′-ATGGAGTCAACCCAGCCTAT-CGCAAGTGAAATCTCCTCCG-3′; MIMIC ets-1-3′, 5′-CCATGCACATGTTGTCTGGG-TCTGTCAATGCAGTTTG-TA-3′.…”

Section: )mentioning

confidence: 99%

“…The first and second PCRs were carried out as previously described. 28,29) The second PCR products were transcribed using T7 RNA polymerase (Gibco BRL, Gaithersberg, MD), and the amount of transcribed internal marker was calculated as previously described. 28,29) Competitive RT-PCR-Southern blot analysis.…”

Section: )mentioning

confidence: 99%

“…28,29) The second PCR products were transcribed using T7 RNA polymerase (Gibco BRL, Gaithersberg, MD), and the amount of transcribed internal marker was calculated as previously described. 28,29) Competitive RT-PCR-Southern blot analysis. Total RNA was isolated from the tissues by means of the acid guanidium thiocyan-A 1 To whom requests for reprints should be addressed.…”

Section: )mentioning

confidence: 99%

“…26,27) ETS-1 acts as an angiogenic mediator in uterine cervical and endometrial cancers. 28,29) These findings prompted us to study whether the proto-oncogene ets-1 acts as an angiogenic mediator in ovarian cancers.…”

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confidence: 99%

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Clinical implications of expression of ETS‐1 in relation to angiogenesis in ovarian cancers

Khatun¹,

Fujimoto²,

Toyoki³

et al. 2003

Cancer Science

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ETS-1 has been identified as a transcription factor involved in tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. This result prompted us to study whether ETS-1 works as an angiogenic mediator in ovarian cancers. Immunohistochemical staining revealed that ETS-1 was expressed in vascular endothelial cells and in cancer cells of ovarian cancers. There was a significant correlation between microvessel counts and both ETS-1 histoscores and ets-1 mRNA levels in ovarian cancers. Both ETS-1 histoscores and ets-1 mRNA levels increased with the progression of ovarian cancers. Furthermore, the 24-month survival rate of 30 patients with high ets-1 (high ETS-1 histoscores and high ets-1 mRNA levels) was 30%, while that of 30 other patients with low ets-1 (low ETS-1 histoscores and ets-1 mRNA levels) was 70%. There was a significant difference between the 24-month survival rates of the 30 patients with high ets-1 and the 30 with low ets-1. This indicates that ETS-1 might act as an angiogenic mediator in, and be a prognostic factor for, ovarian cancers. ngiogenesis is essential for development, growth and progression of solid tumors.1) The angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF; identical with thymidine phosphorylase (TP)), and interleukin (IL)-8 modulate angiogenesis in ovarian cancers.2-5) bFGF was found to be expressed in both cancer and interstitial cells of ovarian cancers, and its levels correlated with clinical stage, but not obviously with the patients' prognosis.2) PD-ECGF was dominantly expressed in interstitial cells of ovarian cancers, and a high level correlated with poor prognosis.3) VEGF, particularly VEGF 165 isomer, was dominantly expressed in cancer cells of primary ovarian cancers, and its level correlated with the patients' prognosis, regardless of histopathological findings.4) Furthermore, patients with higher VEGF levels in peritoneal metastatic lesions than in the primary tumors had poorer prognosis. 5)During angiogenesis, ETS-1 is strongly expressed in vascular endothelial cells and in the adjacent interstitial cells. 6) Once angiogenesis has ended, ETS-1 expression is down-regulated. 7,8) The representative angiogenic factors VEGF and bFGF immediately induce ETS-1 expression in the early stage of angiogenesis, while the inhibition of ETS-1 expression leads to suppression of angiogenesis.9, 10) The proteases urokinase typeplasminogen activator (u-PA), matrix metalloprotease (MMP)-1, MMP-3 and MMP-9 have a conserved ETS-binding motif, and transcription factor ETS-1 converts vascular endothelial cells to angiogenic phenotypes by inducing expression of u-PA, 12) Ets-1 is expressed in various gastric, pancreatic, esophageal, and hepatocellular and cholangiocellular carcinomas and in thyroid and astrocytic tumors, and acts as a proto-oncogene. [13][14][15][16][17][18][19] ETS-1 is up-regulated and involved in the overexpression of MMP-7 in hepa...

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“…28,29) These findings prompted us to study whether the proto-oncogene ets-1 acts as an angiogenic mediator in ovarian cancers.…”

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Clinical implications of expression of ETS‐1 in relation to angiogenesis in ovarian cancers

Khatun¹,

Fujimoto²,

Toyoki³

et al. 2003

Cancer Science

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Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

Shabo

Olsson

Sun

et al. 2009

Intl Journal of Cancer

123

127

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Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n 5 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 3 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p 5 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation. ' 2009 UICC

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Sex Steroid-Dependent and -Independent Angiogenesis in Uterine Endometrial Cancers

Fujimoto

Aoki

Toyoki

et al. 2003

Cell and Molecular Biology of Endometrial Carcinoma

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Clinical implications of expression of ETS-1 related to angiogenesis in uterine cervical cancers

Abstract: ETS-1 might be a prognostic indicator as an angiogenic mediator in uterine cervical cancers.

Cited by 53 publications

References 25 publications

Clinical implications of expression of ETS‐1 in relation to angiogenesis in ovarian cancers

Clinical implications of expression of ETS‐1 in relation to angiogenesis in ovarian cancers

Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

Sex Steroid-Dependent and -Independent Angiogenesis in Uterine Endometrial Cancers

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