Role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated growth by estradiol, prolactin and progesterone in human and rat mammary tumor cells: Studies using TGF-α and EGF receptor antibodies

Syed Rafeeq Ahmed, Betty Badger, Carol Wright, Andrea Manni

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Abstract

The biological role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated proliferation of primary human and rat mammary tumor cells was studied using antibodies against TGF-α and its receptor. A monoclonal antibody, MAb-425 against human EGF receptor was added to in vitro soft agar, clonogenic cultures of human breast carcinoma cells under basal and estradiol(E2)-stimulated conditions. The antibody had an antagonist effect on colony growth in 4 of 10 tumors and an agonist effect in 4 (72 and 153% of control). E2-stimulated colony growth in 5 tumors (167% of control) and the antibody blocked E2-stimulation in 3 of the 5. Inhibition of E2-stimulated growth in 3 and basal growth in 4 other tumors by the EGF receptor antibody suggests that endogenously secreted TGF-α has a role as an autocrine/paracrine growth factor in constitutive and E2-stimulated tumor cell proliferation in a majority of human tumors. A polyclonal antibody against TGF-α was used to study the role of TGF-α in E2-, prolactin(Prl)- and progesterone(Prog)-stimulated proliferation of NMU(nitrosomethylurea)-induced rat mammary tumor cells under similar culture conditions. TGF-α, E2, Prl and Prog stimulated colony growth equally to 176, 187, 168 and 181% of control. The antibody produced significant and similar inhibition of TGF-α and E2-stimulated growth (95 and 83%). In contrast, inhibition of Prl- and Prog-stimulated growth by the antibody was only 24 and 37%. The TGF-α ligand antibody did not have an agonist or antagonist effect when added alone. Thus, TGF-α seems to be a major stimulatory growth factor mediating E2-induced tumor cell proliferation in rat mammary tumors. It is less important in Prl- and Prog-induced tumor growth and not essential for basal growth in these tumors. We conclude that TGF-α is a biologically important autocrine/paracrine growth factor in primary human breast cancer cell proliferation and in E2-induced rat mammary tumor growth.

Original languageEnglish (US)
Pages (from-to)687-693
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume38
Issue number6
DOIs
StatePublished - Jun 1991

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Transforming Growth Factors
Epidermal Growth Factor Receptor
Prolactin
Growth Hormone
Progesterone
Rats
Tumors
Estradiol
Cells
Hormones
Breast Neoplasms
Antibodies
Growth
Neoplasms
Cell proliferation
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Cell culture
Methylnitrosourea
Growth Factor Receptors

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

@article{7c908965d6e5490ab7c9c4001e57ac2c,
title = "Role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated growth by estradiol, prolactin and progesterone in human and rat mammary tumor cells: Studies using TGF-α and EGF receptor antibodies",
abstract = "The biological role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated proliferation of primary human and rat mammary tumor cells was studied using antibodies against TGF-α and its receptor. A monoclonal antibody, MAb-425 against human EGF receptor was added to in vitro soft agar, clonogenic cultures of human breast carcinoma cells under basal and estradiol(E2)-stimulated conditions. The antibody had an antagonist effect on colony growth in 4 of 10 tumors and an agonist effect in 4 (72 and 153{\%} of control). E2-stimulated colony growth in 5 tumors (167{\%} of control) and the antibody blocked E2-stimulation in 3 of the 5. Inhibition of E2-stimulated growth in 3 and basal growth in 4 other tumors by the EGF receptor antibody suggests that endogenously secreted TGF-α has a role as an autocrine/paracrine growth factor in constitutive and E2-stimulated tumor cell proliferation in a majority of human tumors. A polyclonal antibody against TGF-α was used to study the role of TGF-α in E2-, prolactin(Prl)- and progesterone(Prog)-stimulated proliferation of NMU(nitrosomethylurea)-induced rat mammary tumor cells under similar culture conditions. TGF-α, E2, Prl and Prog stimulated colony growth equally to 176, 187, 168 and 181{\%} of control. The antibody produced significant and similar inhibition of TGF-α and E2-stimulated growth (95 and 83{\%}). In contrast, inhibition of Prl- and Prog-stimulated growth by the antibody was only 24 and 37{\%}. The TGF-α ligand antibody did not have an agonist or antagonist effect when added alone. Thus, TGF-α seems to be a major stimulatory growth factor mediating E2-induced tumor cell proliferation in rat mammary tumors. It is less important in Prl- and Prog-induced tumor growth and not essential for basal growth in these tumors. We conclude that TGF-α is a biologically important autocrine/paracrine growth factor in primary human breast cancer cell proliferation and in E2-induced rat mammary tumor growth.",
author = "Ahmed, {Syed Rafeeq} and Betty Badger and Carol Wright and Andrea Manni",
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T1 - Role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated growth by estradiol, prolactin and progesterone in human and rat mammary tumor cells

T2 - Studies using TGF-α and EGF receptor antibodies

AU - Ahmed, Syed Rafeeq

AU - Badger, Betty

AU - Wright, Carol

AU - Manni, Andrea

PY - 1991/6

Y1 - 1991/6

N2 - The biological role of transforming growth factor-α (TGF-α) in basal and hormone-stimulated proliferation of primary human and rat mammary tumor cells was studied using antibodies against TGF-α and its receptor. A monoclonal antibody, MAb-425 against human EGF receptor was added to in vitro soft agar, clonogenic cultures of human breast carcinoma cells under basal and estradiol(E2)-stimulated conditions. The antibody had an antagonist effect on colony growth in 4 of 10 tumors and an agonist effect in 4 (72 and 153% of control). E2-stimulated colony growth in 5 tumors (167% of control) and the antibody blocked E2-stimulation in 3 of the 5. Inhibition of E2-stimulated growth in 3 and basal growth in 4 other tumors by the EGF receptor antibody suggests that endogenously secreted TGF-α has a role as an autocrine/paracrine growth factor in constitutive and E2-stimulated tumor cell proliferation in a majority of human tumors. A polyclonal antibody against TGF-α was used to study the role of TGF-α in E2-, prolactin(Prl)- and progesterone(Prog)-stimulated proliferation of NMU(nitrosomethylurea)-induced rat mammary tumor cells under similar culture conditions. TGF-α, E2, Prl and Prog stimulated colony growth equally to 176, 187, 168 and 181% of control. The antibody produced significant and similar inhibition of TGF-α and E2-stimulated growth (95 and 83%). In contrast, inhibition of Prl- and Prog-stimulated growth by the antibody was only 24 and 37%. The TGF-α ligand antibody did not have an agonist or antagonist effect when added alone. Thus, TGF-α seems to be a major stimulatory growth factor mediating E2-induced tumor cell proliferation in rat mammary tumors. It is less important in Prl- and Prog-induced tumor growth and not essential for basal growth in these tumors. We conclude that TGF-α is a biologically important autocrine/paracrine growth factor in primary human breast cancer cell proliferation and in E2-induced rat mammary tumor growth.

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