Tissue, cell type, and breast cancer stage-specific expression of a TGF- β inducible early transcription factor gene

M. Subramaniam, T. E. Hefferan, K. Tau, D. Peus, M. Pittelkow, S. Jalal, B. L. Riggs, P. Roche, T. C. Spelsberg

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

This laboratory has previously identified a novel TGF-β inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907-4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-β treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods, interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-β1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation.

Original languageEnglish (US)
Pages (from-to)226-236
Number of pages11
JournalJournal of Cellular Biochemistry
Volume68
Issue number2
DOIs
StatePublished - Feb 1 1998

Fingerprint

Genetic Transcription
Transcription Factors
Genes
Tissue
Breast Neoplasms
Osteoblasts
Proteins
Biopsy
Chromosomes
Bone
Breast
Osteopetrosis
Negative Staining
myc Genes
Carcinoma in Situ
Human Chromosomes
Tumor Suppressor Genes
Polymorphism
Keratinocytes
Immunoprecipitation

Keywords

  • Breast cancer stage
  • Immunohistochemistry
  • Osteoblasts
  • Rapid regulation
  • TGF-β
  • Transcription factor
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Tissue, cell type, and breast cancer stage-specific expression of a TGF- β inducible early transcription factor gene. / Subramaniam, M.; Hefferan, T. E.; Tau, K.; Peus, D.; Pittelkow, M.; Jalal, S.; Riggs, B. L.; Roche, P.; Spelsberg, T. C.

In: Journal of Cellular Biochemistry, Vol. 68, No. 2, 01.02.1998, p. 226-236.

Research output: Contribution to journalArticle

Subramaniam, M. ; Hefferan, T. E. ; Tau, K. ; Peus, D. ; Pittelkow, M. ; Jalal, S. ; Riggs, B. L. ; Roche, P. ; Spelsberg, T. C. / Tissue, cell type, and breast cancer stage-specific expression of a TGF- β inducible early transcription factor gene. In: Journal of Cellular Biochemistry. 1998 ; Vol. 68, No. 2. pp. 226-236.
@article{70264517d70a4bf79f556c2a48fa25ae,
title = "Tissue, cell type, and breast cancer stage-specific expression of a TGF- β inducible early transcription factor gene",
abstract = "This laboratory has previously identified a novel TGF-β inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907-4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-β treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods, interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-β1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation.",
keywords = "Breast cancer stage, Immunohistochemistry, Osteoblasts, Rapid regulation, TGF-β, Transcription factor, Tumor suppressor",
author = "M. Subramaniam and Hefferan, {T. E.} and K. Tau and D. Peus and M. Pittelkow and S. Jalal and Riggs, {B. L.} and P. Roche and Spelsberg, {T. C.}",
year = "1998",
month = "2",
day = "1",
doi = "10.1002/(SICI)1097-4644(19980201)68:2<226::AID-JCB9>3.0.CO;2-X",
language = "English (US)",
volume = "68",
pages = "226--236",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Tissue, cell type, and breast cancer stage-specific expression of a TGF- β inducible early transcription factor gene

AU - Subramaniam, M.

AU - Hefferan, T. E.

AU - Tau, K.

AU - Peus, D.

AU - Pittelkow, M.

AU - Jalal, S.

AU - Riggs, B. L.

AU - Roche, P.

AU - Spelsberg, T. C.

PY - 1998/2/1

Y1 - 1998/2/1

N2 - This laboratory has previously identified a novel TGF-β inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907-4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-β treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods, interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-β1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation.

AB - This laboratory has previously identified a novel TGF-β inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907-4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-β treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods, interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-β1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation.

KW - Breast cancer stage

KW - Immunohistochemistry

KW - Osteoblasts

KW - Rapid regulation

KW - TGF-β

KW - Transcription factor

KW - Tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=0031974444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031974444&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4644(19980201)68:2<226::AID-JCB9>3.0.CO;2-X

DO - 10.1002/(SICI)1097-4644(19980201)68:2<226::AID-JCB9>3.0.CO;2-X

M3 - Article

C2 - 9443078

AN - SCOPUS:0031974444

VL - 68

SP - 226

EP - 236

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 2

ER -