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Published on: August 25, 2021

Expression of the NF-kappaB-responsive gene BTG2 is aberrantly regulated in breast cancer

Hirofumi Kawakubo1, Jennifer L Carey, Elena Brachtel

  • 1Department of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Oncogene
|September 21, 2004
PubMed

Insights

BTG2, an antiproliferative gene, is suppressed by hormones during pregnancy and in breast cancer. Loss of BTG2 is an early event in mammary tumor development, suggesting its role in cancer prevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • BTG2 is a p53-inducible gene with antiproliferative functions.
  • NF-kappaB activation stimulates BTG2 in breast cancer cells.
  • Hormonal regulation of BTG2 in mammary gland development is suggested.

Purpose of the Study:

  • To investigate the role of BTG2 in mammary gland development and breast cancer.
  • To explore the relationship between BTG2, hormones, and cell cycle regulators.
  • To assess BTG2 expression in human breast tumors.

Main Methods:

  • Analysis of BTG2 expression in rat mammary glands during pregnancy and lactation.
  • Investigation of BTG2 regulation by estrogen and progestin.
  • Assessment of BTG2's effect on cell cycle progression and cyclin D1 expression.
  • Comparison of BTG2 levels in human breast cancer cell lines and tumors versus normal tissues.
  • Examination of BTG2 protein in a mouse mammary tumor model.

Main Results:

  • BTG2 expression decreased during pregnancy and lactation in rat mammary glands, correlating with increased cyclin D1.
  • Estrogen and progestin suppressed BTG2 expression and stimulated cyclin D1.
  • Ectopic BTG2 expression inhibited breast cancer cell growth by causing G1 arrest, which was reversed by cyclin D1.
  • BTG2 was downregulated in human breast cancer cell lines and tumors.
  • Loss of BTG2 protein was observed early in mammary tumor development in mice.

Conclusions:

  • Hormonal downregulation of BTG2 may contribute to mammary gland proliferation during pregnancy.
  • BTG2 acts as a tumor suppressor by inhibiting cell proliferation and promoting G1 arrest.
  • Deregulation of BTG2 is an early event in mammary tumorigenesis and may be a critical step in breast cancer development.

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