Prolactin and epidermal growth factor regulation of the proliferation, morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture

Kathleen M. Darcy, Suzanne F. Shoemaker, Ping‐Ping H. Lee, Mary M. Vaughan, Jennifer D. Black, Margot M. Ip

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The epithelial cell‐specific effects of prolactin and epidermal growth factor (EGF) on the development of normal rat mammary epithelial cells (MEC) were evaluated using a three dimensional primary culture model developed in our laboratory. Non‐milk‐producing MEC were isolated as spherical end bud‐like mammary epithelial organoids (MEO) from pubescent virgin female rats. The cultured MEO developed into elaborate multilobular and lobuloductal alveolar organoids composed of cytologically and functionally differentiated MEC. Prolactin (0.01–10 μg/ml) and EGF (1–100 ng/ml) were each required for induction of cell growth, extensive alveolar, as well as multilobular branching morphogenesis, and casein accumulation. MEO cultured without prolactin for 14 days remained sensitive to the mitogenic, morphogenic, and lactogenic effects of prolactin upon subsequent exposure. Similarly, cells cultured in the absence of EGF remained sensitive to the mitogenic and lactogenic effects of EGF, but were less responsive to its morphogenic effects when it was added on day 14 of a 21‐day culture period. If exposure to prolactin was terminated after the first week, the magnitude of the mitogenic and lactogenic effects, but not the morphogenic response was decreased. Removal of EGF on day 7 also reduced the mitogenic response, but did not have any effect on the magnitude of the lactogenic or morphogenic responses. These studies demonstrate that physiologically relevant development of normal MEC can be induced in culture and that this model system can be used to study the mechanisms by which prolactin and EGF regulate the complex developmental pathways operative in the mammary gland. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)346-364
Number of pages19
JournalJournal of Cellular Physiology
Volume163
Issue number2
DOIs
StatePublished - May 1995

Fingerprint

Morphogenesis
Epidermal Growth Factor
Prolactin
Rats
Organoids
Breast
Epithelial Cells
Cell growth
Caseins
Human Mammary Glands
Cultured Cells
Growth

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Prolactin and epidermal growth factor regulation of the proliferation, morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture. / Darcy, Kathleen M.; Shoemaker, Suzanne F.; Lee, Ping‐Ping H.; Vaughan, Mary M.; Black, Jennifer D.; Ip, Margot M.

In: Journal of Cellular Physiology, Vol. 163, No. 2, 05.1995, p. 346-364.

Research output: Contribution to journalArticle

@article{b96729aaaaab40a8997ee43e60e7cc4b,
title = "Prolactin and epidermal growth factor regulation of the proliferation, morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture",
abstract = "The epithelial cell‐specific effects of prolactin and epidermal growth factor (EGF) on the development of normal rat mammary epithelial cells (MEC) were evaluated using a three dimensional primary culture model developed in our laboratory. Non‐milk‐producing MEC were isolated as spherical end bud‐like mammary epithelial organoids (MEO) from pubescent virgin female rats. The cultured MEO developed into elaborate multilobular and lobuloductal alveolar organoids composed of cytologically and functionally differentiated MEC. Prolactin (0.01–10 μg/ml) and EGF (1–100 ng/ml) were each required for induction of cell growth, extensive alveolar, as well as multilobular branching morphogenesis, and casein accumulation. MEO cultured without prolactin for 14 days remained sensitive to the mitogenic, morphogenic, and lactogenic effects of prolactin upon subsequent exposure. Similarly, cells cultured in the absence of EGF remained sensitive to the mitogenic and lactogenic effects of EGF, but were less responsive to its morphogenic effects when it was added on day 14 of a 21‐day culture period. If exposure to prolactin was terminated after the first week, the magnitude of the mitogenic and lactogenic effects, but not the morphogenic response was decreased. Removal of EGF on day 7 also reduced the mitogenic response, but did not have any effect on the magnitude of the lactogenic or morphogenic responses. These studies demonstrate that physiologically relevant development of normal MEC can be induced in culture and that this model system can be used to study the mechanisms by which prolactin and EGF regulate the complex developmental pathways operative in the mammary gland. {\circledC} 1995 Wiley‐Liss, Inc.",
author = "Darcy, {Kathleen M.} and Shoemaker, {Suzanne F.} and Lee, {Ping‐Ping H.} and Vaughan, {Mary M.} and Black, {Jennifer D.} and Ip, {Margot M.}",
year = "1995",
month = "5",
doi = "10.1002/jcp.1041630216",
language = "English (US)",
volume = "163",
pages = "346--364",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Prolactin and epidermal growth factor regulation of the proliferation, morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture

AU - Darcy, Kathleen M.

AU - Shoemaker, Suzanne F.

AU - Lee, Ping‐Ping H.

AU - Vaughan, Mary M.

AU - Black, Jennifer D.

AU - Ip, Margot M.

PY - 1995/5

Y1 - 1995/5

N2 - The epithelial cell‐specific effects of prolactin and epidermal growth factor (EGF) on the development of normal rat mammary epithelial cells (MEC) were evaluated using a three dimensional primary culture model developed in our laboratory. Non‐milk‐producing MEC were isolated as spherical end bud‐like mammary epithelial organoids (MEO) from pubescent virgin female rats. The cultured MEO developed into elaborate multilobular and lobuloductal alveolar organoids composed of cytologically and functionally differentiated MEC. Prolactin (0.01–10 μg/ml) and EGF (1–100 ng/ml) were each required for induction of cell growth, extensive alveolar, as well as multilobular branching morphogenesis, and casein accumulation. MEO cultured without prolactin for 14 days remained sensitive to the mitogenic, morphogenic, and lactogenic effects of prolactin upon subsequent exposure. Similarly, cells cultured in the absence of EGF remained sensitive to the mitogenic and lactogenic effects of EGF, but were less responsive to its morphogenic effects when it was added on day 14 of a 21‐day culture period. If exposure to prolactin was terminated after the first week, the magnitude of the mitogenic and lactogenic effects, but not the morphogenic response was decreased. Removal of EGF on day 7 also reduced the mitogenic response, but did not have any effect on the magnitude of the lactogenic or morphogenic responses. These studies demonstrate that physiologically relevant development of normal MEC can be induced in culture and that this model system can be used to study the mechanisms by which prolactin and EGF regulate the complex developmental pathways operative in the mammary gland. © 1995 Wiley‐Liss, Inc.

AB - The epithelial cell‐specific effects of prolactin and epidermal growth factor (EGF) on the development of normal rat mammary epithelial cells (MEC) were evaluated using a three dimensional primary culture model developed in our laboratory. Non‐milk‐producing MEC were isolated as spherical end bud‐like mammary epithelial organoids (MEO) from pubescent virgin female rats. The cultured MEO developed into elaborate multilobular and lobuloductal alveolar organoids composed of cytologically and functionally differentiated MEC. Prolactin (0.01–10 μg/ml) and EGF (1–100 ng/ml) were each required for induction of cell growth, extensive alveolar, as well as multilobular branching morphogenesis, and casein accumulation. MEO cultured without prolactin for 14 days remained sensitive to the mitogenic, morphogenic, and lactogenic effects of prolactin upon subsequent exposure. Similarly, cells cultured in the absence of EGF remained sensitive to the mitogenic and lactogenic effects of EGF, but were less responsive to its morphogenic effects when it was added on day 14 of a 21‐day culture period. If exposure to prolactin was terminated after the first week, the magnitude of the mitogenic and lactogenic effects, but not the morphogenic response was decreased. Removal of EGF on day 7 also reduced the mitogenic response, but did not have any effect on the magnitude of the lactogenic or morphogenic responses. These studies demonstrate that physiologically relevant development of normal MEC can be induced in culture and that this model system can be used to study the mechanisms by which prolactin and EGF regulate the complex developmental pathways operative in the mammary gland. © 1995 Wiley‐Liss, Inc.

UR - http://www.scopus.com/inward/record.url?scp=0028905117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028905117&partnerID=8YFLogxK

U2 - 10.1002/jcp.1041630216

DO - 10.1002/jcp.1041630216

M3 - Article

C2 - 7706378

AN - SCOPUS:0028905117

VL - 163

SP - 346

EP - 364

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -