Nf-κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α

Poornima Bhat-Nakshatri, Thomas R. Newton, Robert Goulet, Harikrishna Nakshatri

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-κB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF- κB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-κB in macrophages and endothelial cells. NF- κB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-κB identified IL-1α as the factor responsible for NF-κB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1α transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1α and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.

Original languageEnglish
Pages (from-to)6971-6976
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number12
DOIs
StatePublished - Jun 9 1998

Fingerprint

Interleukin-1
Estrogen Receptors
Interleukin-6
Fibroblasts
Breast Neoplasms
Conditioned Culture Medium
Neoplasm Metastasis
Angiogenesis Inducing Agents
Plasminogen Activators
Urokinase-Type Plasminogen Activator
Hypercalcemia
Osteoclasts
Extracellular Matrix
Neoplasms
Transcription Factors
Endothelial Cells
Lymph Nodes
Macrophages
Cytokines
Gene Expression

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Nf-κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α. / Bhat-Nakshatri, Poornima; Newton, Thomas R.; Goulet, Robert; Nakshatri, Harikrishna.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 12, 09.06.1998, p. 6971-6976.

Research output: Contribution to journalArticle

@article{520205713d424a18981ddade656c0ffc,
title = "Nf-κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α",
abstract = "Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-κB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF- κB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-κB in macrophages and endothelial cells. NF- κB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-κB identified IL-1α as the factor responsible for NF-κB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1α transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1α and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.",
author = "Poornima Bhat-Nakshatri and Newton, {Thomas R.} and Robert Goulet and Harikrishna Nakshatri",
year = "1998",
month = "6",
day = "9",
doi = "10.1073/pnas.95.12.6971",
language = "English",
volume = "95",
pages = "6971--6976",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "12",

}

TY - JOUR

T1 - Nf-κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α

AU - Bhat-Nakshatri, Poornima

AU - Newton, Thomas R.

AU - Goulet, Robert

AU - Nakshatri, Harikrishna

PY - 1998/6/9

Y1 - 1998/6/9

N2 - Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-κB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF- κB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-κB in macrophages and endothelial cells. NF- κB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-κB identified IL-1α as the factor responsible for NF-κB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1α transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1α and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.

AB - Several angiogenic factors and extracellular matrix-degrading enzymes that promote invasion and metastasis of cancer are produced by stromal fibroblasts that surround cancer cells. The expression of genes that code for some of these proteins is regulated by the transcription factor NF-κB. In this report, we demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but not ER-positive breast cancer cells induces NF- κB in fibroblasts. In contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF-κB in macrophages and endothelial cells. NF- κB activation in fibroblasts was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen activator (uPA), both of which promote angiogenesis and metastasis. A survey of cytokines known for their ability to induce NF-κB identified IL-1α as the factor responsible for NF-κB activation in fibroblasts. Analysis of primary breast carcinomas revealed the presence of IL-1α transcripts in majority of lymph node-positive breast cancers. These results along with the known role of IL-1α and IL-6 in osteoclast formation provide insight into the mechanism of metastasis and hypercalcemia in advanced breast cancers.

UR - http://www.scopus.com/inward/record.url?scp=0032499534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032499534&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.12.6971

DO - 10.1073/pnas.95.12.6971

M3 - Article

VL - 95

SP - 6971

EP - 6976

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 12

ER -