Estrogens play an important role in the growth and terminal differentiation of the mammary gland. Prolonged exposure to estrogens seems to predispose women to breast cancer. It recently became evident that not only the intrinsic hormonal status but also external factors such as the occurrence of pharmaceuticals and chemicals with hormone activity in the environment may put women at greater risk of developing breast cancer. We focused on the interference of endocrine disruptors in breast cancer therapy. We observed that phenol red added to the culture medium strongly promoted the cell proliferation and cell cycle progression of human cells expressing the estrogen receptor, and affected their susceptibility to chemotherapy.
15 August 2009 in Annals of the New York Academy of Sciences
The inhibition of cyclin-dependent kinases (CDKs) represents a novel approach to the therapy of human malignancies. Already in clinical trials, recently developed CDK inhibitors very efficiently target the rapidly proliferating cancer cells and inhibit their cell-cycle progression. Interestingly, some CDK inhibitors additionally affect the stability and activity of the tumour-suppressor protein p53, thereby enhancing their antiproliferative action towards cancer cells. Considering the fact that the p53 protein is mutated or inactivated in ~ 50% of all human cancers, the efficacy of CDK inhibitor therapy could differ between cancer cells depending on their p53 status. Moreover, recent reports demonstrating that some cancer cells can proliferate despite CDK2 inhibition questioned the central role of CDK2 in the cell-cycle control and suitability of CDK2 as a therapeutic target; however, the p53 activation that is mediated by CDK inhibitors could be essential for the efficacy of CDK inhibitors in therapy of ...