Expression of CSF-I and CSF-I receptor by normal lactating mammary epithelial cells

J Soc Gynecol Investig. Mar-Apr 1998;5(2):94-101. doi: 10.1016/S1071-5576(97)00108-1.

Abstract

Objective: Previous studies suggested a potential role for macrophage colony stimulating factor (CSF-1) in lactogenic differentiation of the breast. The aim of this study was to define the regulation of CSF-1 and its receptor (CSF-1R, the product of c-fms proto-oncogene) by lactogenic hormones in the breast in vivo during pregnancy and lactation and in vitro in organ culture and mammary epithelial cell lines.

Methods: Immunohistochemical staining assays for the expression of CSF-1 and CSF-1R antigens were performed on sections of breast biopsies from nonpregnant (n = 10), prepartum (n = 4), and postpartum lactating patients (n = 7) and on sections of human mammary glands cultured in the presence of the lactogenic hormones insulin, prolactin, and glucocorticoids. Northern blot analyses were used to study the regulation of CSF-1 and CSF-1R by these same lactogenic hormones in normal and neoplastic mammary epithelial cell lines in cell culture.

Results: Normal, nonlactating mammary epithelium did not express CSF-1R and synthesized only low levels of CSF-1. During lactation, significant levels of both proteins could be observed in the epithelial cells that line actively lactating ducts and alveoli. Very similar increases in epithelial cell expression of CSF-1 and CSF-1R were observed in organ cultures of normal mammary gland biopsies exposed to prolactin, insulin, and glucocorticoids. Colony stimulating factor mRNA levels were increased by prolactin and/or insulin in a normal mammary epithelial cell line, while glucocorticoids had no apparent effect on CSF-1 mRNA levels. In contrast, we found that the levels of CSF-1R transcript are regulated primarily by glucocorticoids in breast carcinoma cells, while prolactin merely modulates the glucocorticoid effect.

Conclusion: The observed increases in the expression of CSF-1 and its receptor during lactogenesis and the regulation of CSF-1/CSF-1R by lactogenic hormones suggests that this cytokine/receptor pair might play a regulatory role in the cellular events leading to the lactogenic differentiation of mammary epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast / drug effects
  • Breast / metabolism*
  • Breast Neoplasms
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology
  • Humans
  • Insulin / pharmacology
  • Lactation*
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Organ Culture Techniques
  • Pregnancy
  • Prolactin / pharmacology
  • RNA, Messenger / metabolism
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism*
  • Tumor Cells, Cultured

Substances

  • Glucocorticoids
  • Insulin
  • RNA, Messenger
  • Macrophage Colony-Stimulating Factor
  • Prolactin
  • Receptor, Macrophage Colony-Stimulating Factor