Accession Number:

ADA355422

Title:

Control of the Mammary Cell Cycle Clock By Estrogen and Progesterone.

Descriptive Note:

Annual rept. 15 Jul 97-14 Jul 98

Corporate Author:

WHITEHEAD INST FOR BIOMEDICAL RESEARCH CAMBRIDGE MA

Personal Author(s):

Report Date:

1998-08-01

Pagination or Media Count:

19.0

Abstract:

Growth and development of the mammary gland are controlled by the female hormones estrogen and progesterone. These hormones affect breast cancer growth and are targets for hormonal therapy. For this reason, it is important to understand the role of these hormones in the proliferation of mammary epithelial cells. We have characterized how these hormones may be interacting with the cell cycle machinery. The cell cycle machinery orchestrates the events required for cells to proliferate. It is composed of cyclins and their catalytic partners known as cyclin-dependent kinases. We have addresses how estrogen and progesterone affect expression and activities of these cell cycle molecules. We have shown that estrogen can induce cyclin D1 expression and activate cyclin E-cdk2 complexes in breast cancer cells. We have also investigated the relationship between progesterone and cyclin D1 using mice lacking either cyclin D1 or the progesterone receptor. Both strains have a defect in mammary gland development. We postulated that cyclin D1 may be regulated by progesterone during pregnancy. However, mammary glands lacking cyclin D1 responded to progesterone like normal mammary glands. In conclusion, we have studied the role of estrogen and progesterone in regulating the cell cycle of mammary epithelial cells. Understanding the growth-regulatory mechanisms affected by these hormones may lead to new ways of breast cancer therapy.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE