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

Analysis by real-time quantitative PCR

Monica M. Reinholz, Stephen J. Iturria, James N. Ingle, Patrick C. Roche

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Several cytokines including members of the transforming growth factor-beta (TGF-β) and tumor necrosis factor (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 and that this expression pattern contributes to their aggressive and metastatic potential and to their capacity to establish and grow in bone. We, therefore, examined the gene expression pattern of the TGF-β family members (inhibin/activin βA subunit (activin βA), inhibin α subunit, and bone morphogenetic protein-2 (BMP-2)), the TNF family members (receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG)), and osteopontin (OPN) in normal, non-invasive, invasive, and metastatic human breast cancer specimens. The mRNA transcript levels of these genes were quantified by reverse transcription (RT) and fluorescent-based kinetic PCR in 18 normal breast tissues, five ductal carcinoma in situ (DCIS), 24 primary breast tumor tissue, and five distant metastases. The mRNA transcript level of each gene was normalized to the amount of β-actin present in the samples. 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 non-invasive, invasive, and liver metastatic breast tumor tissue compared to normal breast tissue. The gene expression of activin βA, a protein involved in cell proliferation and osteoclast induction, increased in invasive and bone metastatic tumor tissue compared to normal breast tissue. The mRNA level of OPN, a bone matrix protein associated with enhanced malignancy, increased in non-invasive, invasive, and liver and bone metastatic breast tumor tissue 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. These results suggest that differential gene expression of bone-related proteins, especially OPN, activin βA, and BMP-2, by primary breast tumor tissues may play a significant role in the invasiveness and metastatic potential of breast cancer.

Original languageEnglish (US)
Pages (from-to)255-269
Number of pages15
JournalBreast Cancer Research and Treatment
Volume74
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Osteopontin
Transforming Growth Factor beta
Real-Time Polymerase Chain Reaction
Breast Neoplasms
Gene Expression
Breast
Bone Morphogenetic Protein 2
Inhibins
Bone and Bones
RANK Ligand
Messenger RNA
Tumor Necrosis Factor-alpha
Osteogenesis
Neoplasms
Proteins
Neoplasm Metastasis
Osteoprotegerin
Bone Matrix
Carcinoma, Intraductal, Noninfiltrating
Liver

Keywords

  • Activin β-A
  • BMP-2
  • Breast cancer
  • Metastasis
  • OPN

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differential gene expression of TGF-β family members and osteopontin in breast tumor tissue : Analysis by real-time quantitative PCR. / Reinholz, Monica M.; Iturria, Stephen J.; Ingle, James N.; Roche, Patrick C.

In: Breast Cancer Research and Treatment, Vol. 74, No. 3, 2002, p. 255-269.

Research output: Contribution to journalArticle

Reinholz, Monica M. ; Iturria, Stephen J. ; Ingle, James N. ; Roche, Patrick C. / Differential gene expression of TGF-β family members and osteopontin in breast tumor tissue : Analysis by real-time quantitative PCR. In: Breast Cancer Research and Treatment. 2002 ; Vol. 74, No. 3. pp. 255-269.
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