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 language | English |
|---|---|
| Pages (from-to) | 981-989 |
| Number of pages | 9 |
| Journal | Molecular Endocrinology |
| Volume | 4 |
| Issue number | 7 |
| State | Published - Jul 1 1990 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
Cite this
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 journal › Article
}
TY - JOUR
T1 - Transforming growth factor-β induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells
AU - Bronzert, Diane A.
AU - Bates, Susan E.
AU - Sheridan, James P.
AU - Lindsey, Ralph
AU - Valverius, Eva M.
AU - Stampfer, Martha R.
AU - Lippman, Marc E
AU - Dickson, Robert B.
PY - 1990/7/1
Y1 - 1990/7/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0025149506&partnerID=8YFLogxK
M3 - Article
C2 - 2178225
AN - SCOPUS:0025149506
VL - 4
SP - 981
EP - 989
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 7
ER -