Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells

Diane A. Bronzert, Susan E. Bates, James P. Sheridan, Ralph Lindsey, Eva M. Valverius, Martha R. Stampfer, Marc E Lippman, Robert B. Dickson

Research output: Contribution to journalArticle

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Abstract

Platelet-derived growth factor (PDGF) is a potent mitogen in human serum which specifically stimulates the proliferation of mesenchymal cells. We have now examined normal human mammary epithelial cells (HMEC) derived from reduction mammaplasties and grown in a serum-free defined medium. Medium conditioned by HMEC contained a PDGF-like activity that competed with [125I]PDGF for binding to PDGF receptors in normal human fibroblasts. When conditioned media were incubated with antiserum specific for either PDGF-A or PDGF-B, only PDGF-A antiserum was capable of inhibiting binding of conditioned media to PDGF receptors. Using an RNase protection assay, mRNA from normal HMEC was probed for both the PDGF-A and PDGF-B chains. Little or no PDGF-B was found in HMEC strains, while a strong signal was seen with the PDGF-A probe. When HMEC were grown in the presence of transforming growth factor-β (TGFβ) for 48 h, inhibition of growth was observed in association with a 20- to 40-fold stimulation of PDGF-B mRNA and a 2-fold stimulation of PDGF-A mRNA. This mRNA induction was extremely rapid (within 1 h), and secreted PDGF activity was induced 2- to 3-fold. Two other HMEC growth inhibitors and differentiating agents, sodium butyrate and phorbol ester 12-ο-tetradecanoylphorbol-13-acetate, had no effect on PDGF mRNA regulation. The current study suggests that PDGF gene induction is an extremely rapid and specific indicator of TGFβ function regardless of whether TGFβ is acting in a growth stimulatory or inhibitory manner. Any role of PDGF-B in TGFβ modulation of differentiation of normal or malignant mammary gland remains to be determined.

Original languageEnglish
Pages (from-to)981-989
Number of pages9
JournalMolecular Endocrinology
Volume4
Issue number7
StatePublished - Jul 1 1990
Externally publishedYes

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Platelet-Derived Growth Factor
Transforming Growth Factors
Proto-Oncogene Proteins c-sis
Breast
Epithelial Cells
Messenger RNA
Growth
Conditioned Culture Medium
Platelet-Derived Growth Factor Receptors
Immune Sera
Growth Inhibitors
Butyric Acid
Mammaplasty
Serum-Free Culture Media
Phorbol Esters
Tetradecanoylphorbol Acetate
Human Mammary Glands
Ribonucleases
Mitogens
Fibroblasts

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Bronzert, D. A., Bates, S. E., Sheridan, J. P., Lindsey, R., Valverius, E. M., Stampfer, M. R., ... Dickson, R. B. (1990). Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells. Molecular Endocrinology, 4(7), 981-989.

Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells. / Bronzert, Diane A.; Bates, Susan E.; Sheridan, James P.; Lindsey, Ralph; Valverius, Eva M.; Stampfer, Martha R.; Lippman, Marc E; Dickson, Robert B.

In: Molecular Endocrinology, Vol. 4, No. 7, 01.07.1990, p. 981-989.

Research output: Contribution to journalArticle

Bronzert, DA, Bates, SE, Sheridan, JP, Lindsey, R, Valverius, EM, Stampfer, MR, Lippman, ME & Dickson, RB 1990, 'Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells', Molecular Endocrinology, vol. 4, no. 7, pp. 981-989.
Bronzert, Diane A. ; Bates, Susan E. ; Sheridan, James P. ; Lindsey, Ralph ; Valverius, Eva M. ; Stampfer, Martha R. ; Lippman, Marc E ; Dickson, Robert B. / Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells. In: Molecular Endocrinology. 1990 ; Vol. 4, No. 7. pp. 981-989.
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