Time-related effects of estrogen withdrawal on proliferation- and cell death-related events in MCF-7 xenografts
Autor: | Cheryl Gillett, Janine Salter, Margaret Hills, Roger A'Hern, Stephen R. D. Johnston, Diana M. Barnes, Simone Detre, Mitch Dowsett, Sharon Riddler |
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Rok vydání: | 1999 |
Předmět: |
Cancer Research
medicine.medical_specialty Programmed cell death Time Factors medicine.drug_class Transplantation Heterologous Mammary gland Mice Nude Estrogen receptor Breast Neoplasms Biology Mice Cyclin D1 Internal medicine Progesterone receptor Tumor Cells Cultured medicine Animals Humans skin and connective tissue diseases Cell Death Estradiol Mammary Neoplasms Experimental Immunohistochemistry Substance Withdrawal Syndrome medicine.anatomical_structure Endocrinology Oncology Estrogen Apoptosis Female Cell Division hormones hormone substitutes and hormone antagonists Hormone |
Zdroj: | International Journal of Cancer. 81:309-313 |
ISSN: | 1097-0215 0020-7136 |
Popis: | Endocrine treatments for human breast cancer have been based largely upon the removal of estrogenic stimuli. The regression of tumors after estrogen deprivation has generally been characterized as being due to reduced proliferation but more recently has been recognized to also involve increased apoptosis. The aim of our experiments was to define the associated changes in certain proliferation- and cell death-related biological parameters after hormone withdrawal from estrogen-dependent MCF-7 xenografts in athymic nude mice using immunohistochemical techniques. The baseline estrogen receptor (ER) level of this MCF-7 xenograft was relatively low (average H score 23) but it was strongly Bcl-2-, PgR- and pS2-positive, indicating the functional integrity of estrogen signaling. Changes in proliferation (Ki-67), apoptosis, ER, progesterone receptor (PgR), cyclin D1, p27kip1, Bcl-2 and Bax expression were assessed during the 2 weeks after estrogen deprivation. ER levels rose markedly after estrogen ablation, whereas PgR levels fell to about 10% of baseline and pS2 levels halved. The proportion of Ki-67-positive cells was unchanged after 24 hr but by day 14 had reduced by about 80%. The normal levels of cyclin D1 also reduced after estrogen withdrawal in contrast to the rapid increase in levels of cyclin-dependent kinase inhibitor p27kip1. This latter increase appeared to occur in advance of the changes in Ki-67. The proportion of apoptotic cells increased from a mean 1.5% at baseline to 2.9% after 3 days and 4.7% after 14 days. There were reductions in both Bcl-2 and Bax staining but these appeared to be greater for Bcl-2, effectively decreasing the Bcl-2/Bax ratio. Our results provide a framework for the use of these parameters as intermediate markers in comparisons of hormonal agents for human breast cancer treatment. |
Databáze: | OpenAIRE |
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