c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer

Marije M. Vleugel, Astrid E. Greijer, Reinhard Bos, Elsken van der Wall, Paul J. van Diest

Research output: Contribution to journalArticle

Abstract

c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and activate c-Jun-dependent transcription. Therefore, activated c-Jun potentially plays an important role in carcinogenesis and cancer progression. To evaluate expression patterns of activated c-Jun in breast cancer in relation to angiogenesis and proliferation, we performed immunohistochemistry on 103 cases of invasive breast cancer with an antibody recognizing phosphorylated c-Jun at serine 73. Activated c-Jun showed a predominantly nuclear expression at the invasive front in 38% of invasive breast cancer cases. Furthermore, expression of activated c-Jun was seen in mitotic cells of the invasive front in 50% of cases. Occasionally, fibroblasts, endothelial cells, and benign breast cells showed nuclear expression. Activated nuclear c-Jun expression showed positive correlations with expression of hyperphosphorylated pRb, vascular endothelial growth factor, and with microvessel density. Mitotic c-Jun expression was associated with pRb and microvessel density. Stromal c-Jun expression showed positive relations with microvessel density. In survival analysis, no significant relation was found with activated c-Jun expression and survival, although a trend with poor survival was found for mitotic cells overexpressing activated c-Jun (P = .09). Our results show that activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation and angiogenesis. Earlier studies have established a functional, in vitro link between activated c-Jun and tumor angiogenesis. Our present results in breast cancer patients confirm this relation in vivo for the first time. Therefore, c-Jun/AP-1 targeting may provide new ways to block tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)668-674
Number of pages7
JournalHuman Pathology
Volume37
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Breast Neoplasms
Transcription Factor AP-1
Microvessels
Serine
Proto-Oncogene Proteins c-jun
Neoplasms
Survival
Oncogene Proteins
Transforming Growth Factors
Protein Transport
Survival Analysis
Vascular Endothelial Growth Factor A
Carcinogenesis
Breast
Transcription Factors
Endothelial Cells
Fibroblasts
Immunohistochemistry
Phosphorylation
Antibodies

Keywords

  • Angiogenesis
  • AP-1
  • Breast cancer
  • c-Jun
  • Immunohistochemistry
  • Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Vleugel, M. M., Greijer, A. E., Bos, R., van der Wall, E., & van Diest, P. J. (2006). c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer. Human Pathology, 37(6), 668-674. https://doi.org/10.1016/j.humpath.2006.01.022

c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer. / Vleugel, Marije M.; Greijer, Astrid E.; Bos, Reinhard; van der Wall, Elsken; van Diest, Paul J.

In: Human Pathology, Vol. 37, No. 6, 06.2006, p. 668-674.

Research output: Contribution to journalArticle

Vleugel, MM, Greijer, AE, Bos, R, van der Wall, E & van Diest, PJ 2006, 'c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer', Human Pathology, vol. 37, no. 6, pp. 668-674. https://doi.org/10.1016/j.humpath.2006.01.022
Vleugel, Marije M. ; Greijer, Astrid E. ; Bos, Reinhard ; van der Wall, Elsken ; van Diest, Paul J. / c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer. In: Human Pathology. 2006 ; Vol. 37, No. 6. pp. 668-674.
@article{8c0f98807e53407896428090c6820866,
title = "c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer",
abstract = "c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and activate c-Jun-dependent transcription. Therefore, activated c-Jun potentially plays an important role in carcinogenesis and cancer progression. To evaluate expression patterns of activated c-Jun in breast cancer in relation to angiogenesis and proliferation, we performed immunohistochemistry on 103 cases of invasive breast cancer with an antibody recognizing phosphorylated c-Jun at serine 73. Activated c-Jun showed a predominantly nuclear expression at the invasive front in 38{\%} of invasive breast cancer cases. Furthermore, expression of activated c-Jun was seen in mitotic cells of the invasive front in 50{\%} of cases. Occasionally, fibroblasts, endothelial cells, and benign breast cells showed nuclear expression. Activated nuclear c-Jun expression showed positive correlations with expression of hyperphosphorylated pRb, vascular endothelial growth factor, and with microvessel density. Mitotic c-Jun expression was associated with pRb and microvessel density. Stromal c-Jun expression showed positive relations with microvessel density. In survival analysis, no significant relation was found with activated c-Jun expression and survival, although a trend with poor survival was found for mitotic cells overexpressing activated c-Jun (P = .09). Our results show that activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation and angiogenesis. Earlier studies have established a functional, in vitro link between activated c-Jun and tumor angiogenesis. Our present results in breast cancer patients confirm this relation in vivo for the first time. Therefore, c-Jun/AP-1 targeting may provide new ways to block tumor angiogenesis.",
keywords = "Angiogenesis, AP-1, Breast cancer, c-Jun, Immunohistochemistry, Proliferation",
author = "Vleugel, {Marije M.} and Greijer, {Astrid E.} and Reinhard Bos and {van der Wall}, Elsken and {van Diest}, {Paul J.}",
year = "2006",
month = "6",
doi = "10.1016/j.humpath.2006.01.022",
language = "English (US)",
volume = "37",
pages = "668--674",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer

AU - Vleugel, Marije M.

AU - Greijer, Astrid E.

AU - Bos, Reinhard

AU - van der Wall, Elsken

AU - van Diest, Paul J.

PY - 2006/6

Y1 - 2006/6

N2 - c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and activate c-Jun-dependent transcription. Therefore, activated c-Jun potentially plays an important role in carcinogenesis and cancer progression. To evaluate expression patterns of activated c-Jun in breast cancer in relation to angiogenesis and proliferation, we performed immunohistochemistry on 103 cases of invasive breast cancer with an antibody recognizing phosphorylated c-Jun at serine 73. Activated c-Jun showed a predominantly nuclear expression at the invasive front in 38% of invasive breast cancer cases. Furthermore, expression of activated c-Jun was seen in mitotic cells of the invasive front in 50% of cases. Occasionally, fibroblasts, endothelial cells, and benign breast cells showed nuclear expression. Activated nuclear c-Jun expression showed positive correlations with expression of hyperphosphorylated pRb, vascular endothelial growth factor, and with microvessel density. Mitotic c-Jun expression was associated with pRb and microvessel density. Stromal c-Jun expression showed positive relations with microvessel density. In survival analysis, no significant relation was found with activated c-Jun expression and survival, although a trend with poor survival was found for mitotic cells overexpressing activated c-Jun (P = .09). Our results show that activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation and angiogenesis. Earlier studies have established a functional, in vitro link between activated c-Jun and tumor angiogenesis. Our present results in breast cancer patients confirm this relation in vivo for the first time. Therefore, c-Jun/AP-1 targeting may provide new ways to block tumor angiogenesis.

AB - c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and activate c-Jun-dependent transcription. Therefore, activated c-Jun potentially plays an important role in carcinogenesis and cancer progression. To evaluate expression patterns of activated c-Jun in breast cancer in relation to angiogenesis and proliferation, we performed immunohistochemistry on 103 cases of invasive breast cancer with an antibody recognizing phosphorylated c-Jun at serine 73. Activated c-Jun showed a predominantly nuclear expression at the invasive front in 38% of invasive breast cancer cases. Furthermore, expression of activated c-Jun was seen in mitotic cells of the invasive front in 50% of cases. Occasionally, fibroblasts, endothelial cells, and benign breast cells showed nuclear expression. Activated nuclear c-Jun expression showed positive correlations with expression of hyperphosphorylated pRb, vascular endothelial growth factor, and with microvessel density. Mitotic c-Jun expression was associated with pRb and microvessel density. Stromal c-Jun expression showed positive relations with microvessel density. In survival analysis, no significant relation was found with activated c-Jun expression and survival, although a trend with poor survival was found for mitotic cells overexpressing activated c-Jun (P = .09). Our results show that activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation and angiogenesis. Earlier studies have established a functional, in vitro link between activated c-Jun and tumor angiogenesis. Our present results in breast cancer patients confirm this relation in vivo for the first time. Therefore, c-Jun/AP-1 targeting may provide new ways to block tumor angiogenesis.

KW - Angiogenesis

KW - AP-1

KW - Breast cancer

KW - c-Jun

KW - Immunohistochemistry

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=33745441050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745441050&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2006.01.022

DO - 10.1016/j.humpath.2006.01.022

M3 - Article

C2 - 16733206

AN - SCOPUS:33745441050

VL - 37

SP - 668

EP - 674

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 6

ER -