Differential gene expression of selective TGF-β family members and osteopontin in breast tumor tissue: Analysis by real-time quantitative PCR

M. M. Reinholz, S. J. Iturria, E. A. Perez, J. N. Ingle, P. C. Roche

Research output: Contribution to journalArticle

Abstract

Several cytokines including members of the TGF-β and TNF families have been implicated in the homing mechanism of breast cancer metastasis. We hypothesize that primary breast tumor tissues differentially express modulators of bone cell function that contribute to their aggressive and metastatic potential and to their capacity to establish and grow in bone. We examined the gene expression pattern of the TGF-β family members (activin β-A subunit, inhibin α subunit, and bone morhogenetic protein-2 (BMP-2)), the TNF family members (receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG)), as well as osteopontin (OPN) in normal, non-invasive, invasive, and metastatic human breast cancer specimens. Methods: The level of mRNA transcripts of these genes in 18 normal breast tissues, 5 ductal carcinoma in situ (DCIS), 24 primary breast tumor tissues, and 5 distant metastases were quantitated by reverse transcription (RT) and fluorescent-based kinetic PCR. Results: We observed differential gene expression of the selected TGF-β family members as well as OPN in breast cancer progression. The average gene expression of the putative tumor suppressor, inhibin α, did not significantly change in any of the tumor tissues examined compared to normal breast tissue. The mRNA level of BMP-2, a protein with anti-proliferative effects in breast cancer cell lines and involved in bone formation, significantly decreased in the different stage breast tumor tissues compared to normal breast tissue. Gene expression of activin β-A, a protein involved in cell proliferation and osteoclast induction, increased in invasive tumor tissue and bone metastasis compared to normal and non-invasive breast tissue. The mRNA level of OPN. a bone matrix protein associated with enhanced malignancy, increased in DCIS. primary tumor tissue, and liver and bone metastases compared to normal breast tissue. In contrast, the average gene expressions of the TNF family members. RANKL and OPG. proteins involved in the regulation of osteoclastogenesis. were only slightly if at all changed in the different stage breast tumor tissues. Conclusion: These results suggest that the TGF-β pathway and OPN may play a more significant role than the TNF pathway in breast cancer invasiveness, metastases and its ability to establish and grow in bone.

Original languageEnglish (US)
Pages (from-to)296
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - 2001

Fingerprint

Osteopontin
Real-Time Polymerase Chain Reaction
Breast Neoplasms
Gene Expression
Bone and Bones
Breast
Neoplasm Metastasis
RANK Ligand
Inhibins
Proteins
Carcinoma, Intraductal, Noninfiltrating
NF-kappa B
Neoplasms
Osteogenesis
Messenger RNA
Bone Matrix
Aptitude
Osteoclasts
Reverse Transcription
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differential gene expression of selective TGF-β family members and osteopontin in breast tumor tissue : Analysis by real-time quantitative PCR. / Reinholz, M. M.; Iturria, S. J.; Perez, E. A.; Ingle, J. N.; Roche, P. C.

In: Breast Cancer Research and Treatment, Vol. 69, No. 3, 2001, p. 296.

Research output: Contribution to journalArticle

@article{a4c018001bb04c86a264a1dc2c1ad45a,
title = "Differential gene expression of selective TGF-β family members and osteopontin in breast tumor tissue: Analysis by real-time quantitative PCR",
abstract = "Several cytokines including members of the TGF-β and TNF families have been implicated in the homing mechanism of breast cancer metastasis. We hypothesize that primary breast tumor tissues differentially express modulators of bone cell function that contribute to their aggressive and metastatic potential and to their capacity to establish and grow in bone. We examined the gene expression pattern of the TGF-β family members (activin β-A subunit, inhibin α subunit, and bone morhogenetic protein-2 (BMP-2)), the TNF family members (receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG)), as well as osteopontin (OPN) in normal, non-invasive, invasive, and metastatic human breast cancer specimens. Methods: The level of mRNA transcripts of these genes in 18 normal breast tissues, 5 ductal carcinoma in situ (DCIS), 24 primary breast tumor tissues, and 5 distant metastases were quantitated by reverse transcription (RT) and fluorescent-based kinetic PCR. Results: We observed differential gene expression of the selected TGF-β family members as well as OPN in breast cancer progression. The average gene expression of the putative tumor suppressor, inhibin α, did not significantly change in any of the tumor tissues examined compared to normal breast tissue. The mRNA level of BMP-2, a protein with anti-proliferative effects in breast cancer cell lines and involved in bone formation, significantly decreased in the different stage breast tumor tissues compared to normal breast tissue. Gene expression of activin β-A, a protein involved in cell proliferation and osteoclast induction, increased in invasive tumor tissue and bone metastasis compared to normal and non-invasive breast tissue. The mRNA level of OPN. a bone matrix protein associated with enhanced malignancy, increased in DCIS. primary tumor tissue, and liver and bone metastases compared to normal breast tissue. In contrast, the average gene expressions of the TNF family members. RANKL and OPG. proteins involved in the regulation of osteoclastogenesis. were only slightly if at all changed in the different stage breast tumor tissues. Conclusion: These results suggest that the TGF-β pathway and OPN may play a more significant role than the TNF pathway in breast cancer invasiveness, metastases and its ability to establish and grow in bone.",
author = "Reinholz, {M. M.} and Iturria, {S. J.} and Perez, {E. A.} and Ingle, {J. N.} and Roche, {P. C.}",
year = "2001",
language = "English (US)",
volume = "69",
pages = "296",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Differential gene expression of selective TGF-β family members and osteopontin in breast tumor tissue

T2 - Analysis by real-time quantitative PCR

AU - Reinholz, M. M.

AU - Iturria, S. J.

AU - Perez, E. A.

AU - Ingle, J. N.

AU - Roche, P. C.

PY - 2001

Y1 - 2001

N2 - Several cytokines including members of the TGF-β and TNF families have been implicated in the homing mechanism of breast cancer metastasis. We hypothesize that primary breast tumor tissues differentially express modulators of bone cell function that contribute to their aggressive and metastatic potential and to their capacity to establish and grow in bone. We examined the gene expression pattern of the TGF-β family members (activin β-A subunit, inhibin α subunit, and bone morhogenetic protein-2 (BMP-2)), the TNF family members (receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG)), as well as osteopontin (OPN) in normal, non-invasive, invasive, and metastatic human breast cancer specimens. Methods: The level of mRNA transcripts of these genes in 18 normal breast tissues, 5 ductal carcinoma in situ (DCIS), 24 primary breast tumor tissues, and 5 distant metastases were quantitated by reverse transcription (RT) and fluorescent-based kinetic PCR. Results: We observed differential gene expression of the selected TGF-β family members as well as OPN in breast cancer progression. The average gene expression of the putative tumor suppressor, inhibin α, did not significantly change in any of the tumor tissues examined compared to normal breast tissue. The mRNA level of BMP-2, a protein with anti-proliferative effects in breast cancer cell lines and involved in bone formation, significantly decreased in the different stage breast tumor tissues compared to normal breast tissue. Gene expression of activin β-A, a protein involved in cell proliferation and osteoclast induction, increased in invasive tumor tissue and bone metastasis compared to normal and non-invasive breast tissue. The mRNA level of OPN. a bone matrix protein associated with enhanced malignancy, increased in DCIS. primary tumor tissue, and liver and bone metastases compared to normal breast tissue. In contrast, the average gene expressions of the TNF family members. RANKL and OPG. proteins involved in the regulation of osteoclastogenesis. were only slightly if at all changed in the different stage breast tumor tissues. Conclusion: These results suggest that the TGF-β pathway and OPN may play a more significant role than the TNF pathway in breast cancer invasiveness, metastases and its ability to establish and grow in bone.

AB - Several cytokines including members of the TGF-β and TNF families have been implicated in the homing mechanism of breast cancer metastasis. We hypothesize that primary breast tumor tissues differentially express modulators of bone cell function that contribute to their aggressive and metastatic potential and to their capacity to establish and grow in bone. We examined the gene expression pattern of the TGF-β family members (activin β-A subunit, inhibin α subunit, and bone morhogenetic protein-2 (BMP-2)), the TNF family members (receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG)), as well as osteopontin (OPN) in normal, non-invasive, invasive, and metastatic human breast cancer specimens. Methods: The level of mRNA transcripts of these genes in 18 normal breast tissues, 5 ductal carcinoma in situ (DCIS), 24 primary breast tumor tissues, and 5 distant metastases were quantitated by reverse transcription (RT) and fluorescent-based kinetic PCR. Results: We observed differential gene expression of the selected TGF-β family members as well as OPN in breast cancer progression. The average gene expression of the putative tumor suppressor, inhibin α, did not significantly change in any of the tumor tissues examined compared to normal breast tissue. The mRNA level of BMP-2, a protein with anti-proliferative effects in breast cancer cell lines and involved in bone formation, significantly decreased in the different stage breast tumor tissues compared to normal breast tissue. Gene expression of activin β-A, a protein involved in cell proliferation and osteoclast induction, increased in invasive tumor tissue and bone metastasis compared to normal and non-invasive breast tissue. The mRNA level of OPN. a bone matrix protein associated with enhanced malignancy, increased in DCIS. primary tumor tissue, and liver and bone metastases compared to normal breast tissue. In contrast, the average gene expressions of the TNF family members. RANKL and OPG. proteins involved in the regulation of osteoclastogenesis. were only slightly if at all changed in the different stage breast tumor tissues. Conclusion: These results suggest that the TGF-β pathway and OPN may play a more significant role than the TNF pathway in breast cancer invasiveness, metastases and its ability to establish and grow in bone.

UR - http://www.scopus.com/inward/record.url?scp=33749101609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749101609&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749101609

VL - 69

SP - 296

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -