Endocrine disrupting chemicals (EDCs) have detrimental effects on human health. Among these EDCs, bisphenol A (BPA) binds to estrogen receptors (ERs) to stimulate estrogen-mediated responses. BPA is assumed to disrupt the reproductive and developmental system of humans. In addition, BPA has recently been suspected as a risk of carcinogenesis. Because BPA can cause abnormal estrogen-mediated response in the organism, exposure to BPA may stimulate growth of estrogen-dependent breast cancers in human. In breast cancer, cyclin E and cyclin-dependent kinase inhibitor p27 are important in G1/S phase transition during cell cycle progression. In this study, using an MTT assay, we investigated the effect of BPA on proliferation of MCF-7 breast cancer cells in vitro. In addition, we also analyzed the transcriptional levels of cyclin E and p27 following treatment with BPA using semi-quantitative RT-PCR. As a result, treatment with BPA resulted in significant induction of breast cancer cell growth, compared to a vehicle. BPA caused alterations of cyclin E and p27 mRNA expression. Expression of cyclin E was increased by BPA, while p27 was decreased at 24 h after treatment with BPA in MCF-7 breast cancer cells. Taken together, these collective results suggest that exposure to BPA induced breast cancer cell proliferation with deregulation of the cell cycle. A further study is required in order to determine the effects of BPA on the carcinogenic process in in vivo models.

It is well known that the imbalance between epithelial cell growth and inhibitor factors may cause human epithelial cancer. Over-expression of the epidermal growth factor receptor(EGFR) has been implicated in the development of oral squamous cell carcinoma. ZD1839 inhibits selectively the EGFR tyrosine kinase activity and is clinically used for cancer patients. However the mechanisms by which it exerts its anti-tumor activity remains unclear. This study attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level and to characterize the effects of ZD1839 with regard to human oral squamous cell carcinoma(OSCC) cell growth. The YD-10B and YD-38 cell lines established from OSCC in the department of Oral Pathology, Yonsei University College of Dentistry and ZD1839(Iressa) were used for this study. The inhibition of cell proliferation induced by ZD1839 was reversible and the lowest dose of ZD1839 that produced statistically significant growth inhibition in YD cell lines were 0.1 μM. The delay in cell cycle progression was induced by 0.1 μM of ZD1839 treatment after 24 hr. This reduction in cell proliferation and cell cycle delay were associated with up-regulation of the cyclin dependent kinase inhibitor(CDKI), P21CIP1/WAF1 and P27KIP1. Reduced expression of cyclin D1 was also observed after treatment with ZD 1839 to YD-38 cells but not to YD-38. The present results suggest that the antiproliferative effects of ZD1839, in vitro was associated with degradation of cyclin D1, which may be used as a possible indicator of a high cell sensitivity to ZD1839.