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Steroidal regulation of cell cycle progression
R L Sutherland1, J A Hamilton, K J Sweeney
1Cancer Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
Abstract:
Sex steroid hormones and their antagonists have well-defined mitogenic and growth-inhibitory effects on target cells including cancer cells. These effects are mediated by cell cycle phase-specific actions, implying that steroids control rates of cell cycle progression by regulating the expression of key cell cycle regulatory genes. An emerging model of cell cycle control involves transcriptional induction of cyclin genes and consequent activation of cyclin-dependent kinases, which initiate cellular events necessary to complete checkpoints within the cell cycle. Our recent studies have focused on the roles of G1 cyclins, particularly cyclin D1, in the control of cell cycle progression in human breast cancer cells. These studies show that cyclin D1 induction is an early response to mitogenic stimulation by oestrogens and progestins, is rate-limiting for G1 progression and is sufficient for completion of the cell cycle in cells arrested in early G1 phase by serum deprivation. Furthermore, inhibition of cyclin D1 expression is an early response to growth-inhibitory anti-oestrogens. These results suggest that cyclin D1 is a target for regulation of cell cycle progression by sex steroids and their antagonists.
Insights
Sex steroids regulate cell cycle progression in breast cancer by controlling cyclin D1 expression. This key protein
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Sex steroid hormones and antagonists impact cell proliferation in cancer.
- Cell cycle progression is regulated by specific genes and proteins.
- Cyclin D1 is a key regulator in the cell cycle.
Purpose of the Study:
- To investigate the role of cyclin D1 in human breast cancer cell cycle control.
- To determine how sex steroids and their antagonists influence cyclin D1 expression.
- To understand the impact of cyclin D1 on cell cycle progression.
Main Methods:
- Studied human breast cancer cells.
- Analyzed cell cycle progression.
- Measured cyclin D1 gene expression.
- Investigated responses to oestrogens, progestins, and anti-oestrogens.
Main Results:
- Cyclin D1 induction is an early response to oestrogen and progestin stimulation.
- Cyclin D1 expression is rate-limiting for G1 phase progression.
- Inhibition of cyclin D1 expression occurs with anti-oestrogen treatment.
- Cyclin D1 is sufficient for cell cycle completion in G1-arrested cells.
Conclusions:
- Cyclin D1 is a critical mediator of sex steroid hormone action on breast cancer cell cycle progression.
- Targeting cyclin D1 may offer therapeutic strategies for hormone-dependent breast cancers.
- Sex steroids and antagonists modulate breast cancer cell growth via cyclin D1 regulation.