Waterpipe smoking is an ancient method of tobacco smoking practiced worldwide. There is a common belief that waterpipe smoking is a safer alternative to cigarette, but many studies showed that some toxicants were associated with cancer risk, significantly higher in waterpipe smoking. Thus, this study aimed to evaluate the status of waterpipe smoker's buccal cells and its cancer risk using the buccal micronucleus cytome test. Forty waterpipe smokers (noncigarette smokers) were recruited and paired by gender, age and alcoholic habits with 40 control subjects. One-thousand cells from each individual were analysed and the number of pyknotic cells (PYC), karyolitic cells (KYL), karyorrhetic cells (KHC), condensed chromatin (CC), binucleated cells (BN), basal cells (BC), nuclear buds (NBUD) and differentiated cells (DIFF) were counted. Additionally, 2000 differentiated cells were analysed counting micronucleated cells (MNi) and nuclear buds. We observed an increasing < 0.05 in all waterpipe smoker's cell parameters, except DIFF (fold-decrease). Only CC showed no differences between groups. The interference in the cell cycle plus DNA damage observed in this study could be responsible for the high number of damaged cells and in death process, showing the importance of our study and the high risk in waterpipe smoking.
Master transcription factors control the transcriptional program and are essential to maintain cellular functions. Among them, steroid nuclear receptors, such as the estrogen receptor α (ERα), are central to the etiology of hormone-dependent cancers which are accordingly treated with corresponding endocrine therapies. However, resistance invariably arises. Here, we show that high levels of the stress response master regulator, the heat shock factor 1 (HSF1), are associated with antiestrogen resistance in breast cancer cells. Indeed, overexpression of HSF1 leads to ERα degradation, decreased expression of ERα-activated genes, and antiestrogen resistance. Furthermore, we demonstrate that reducing HSF1 levels reinstates expression of the ERα and restores response to antiestrogens. Last, our results establish a proof of concept that inhibition of HSF1, in combination with antiestrogens, is a valid strategy to tackle resistant breast cancers. Taken together, we are proposing a mechanism where high HSF1 levels interfere with the ERα-dependent transcriptional program leading to endocrine resistance in breast cancer.
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