Abstract
The impact of estrogens (E) and progestins (P) on the breast is crucial. Recent epidemiological
studies raised a great concern concerning breast cancer risk and hormone replacement
therapy (HRT). However, the effects of HRT in breast tissue remain unclear. Biological
data predominantly show that P are antiproliferative and proapoptotic at least for
normal breast cells. These antiproliferative effects of P are well described at the
cellular level. Whereas E2 increases the level of the various cyclins involved in
the cell cycle progression and decreases the cyclin kinase inhibitors, p21 and p27,
progestins act in an opposite manner. In addition, they both modulate the phosphorylated
rate of Rb involved into the S phase progression. Various proteins of the apoptotic
cascade are also targets for E2 and P. We showed that bcl-2, p53 and caspase 3 are
oppositely modulated by E2 and P in normal and breast cancer cell cultures.
It is very possible that in vivo the balance between E2/P, the type of P, specific
phenotypes could explain increasing risk during HRT, which appears to be mainly a
promoter effect on preexisting transformed cells.
Keywords
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Article info
Publication history
Accepted:
June 10,
2004
Received in revised form:
May 18,
2004
Received:
December 16,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
