RESUMEN
HOX genes encode a family of transcriptional regulators that are involved in pattern formation and organogenesis during embryo development. In addition, these genes play important roles in adult tissues and some of the dysregulated HOX genes are associated with cancer development and metastasis. Like many other HOX genes, HOXC9 is aberrantly expressed in certain breast cancer cell lines and tissues; however, its specific functions in breast cancer progression were not investigated. In the present study, we demonstrated that HOXC9 overexpression in breast cancer cell lines such as MDA-MB-231 and MCF7 increased the invasiveness but reduced the proliferation of cells, resembling a phenotype switch from a proliferative to an invasive state. Furthermore, the reciprocal result was detected in MCF7 and BT474 cells when the expression level of HOXC9 was reduced with siRNA. The clinical impact of HOXC9 in breast cancer was interpreted from the survival analysis data, in which high HOXC9 expression led to considerably poorer disease-free survival and distant metastasis-free survival, especially in lymph node-positive patients. Together, the prognostic relevance of HOXC9 and the HOXC9-derived phenotypic switch between proliferative and invasive states in the breast cancer cell lines suggest that HOXC9 could be a prognostic marker in breast cancer patients with lymph node metastasis and a target for therapeutic intervention in malignant breast cancer.
RESUMEN
Saccharomyces cerevisiae is a well-established model organism to study the mechanisms of longevity. One of the two aging paradigms studied in yeast is termed chronological lifespan (CLS). CLS is defined by the amount of time non-dividing yeast cells can survive at stationary phase. Here, we propose new approaches that allow rapid and efficient quantification of survival rates in aging yeast cultures using either a fluorescent cell counter or microplate imaging. We have generated a software called analysr (Analytical Algorithm for Yeast Survival Rates) that allows automated and highly reproducible analysis of cell survival in aging yeast cultures using fluorescent data. To demonstrate the efficiency of our new experimental tools, we tested the previously characterized ability of caloric restriction to extend lifespan. Interestingly, we found that this process is independent of the expression of three central yeast heat shock proteins (Hsp26, Hsp42, Hsp104). Finally, our new assay is easily adaptable to other types of toxicity studies. Here, we assessed the toxicity of various concentrations of acetic acid, a known contributor of yeast chronological aging. These assays provide researchers with cost-effective, low- and high-content assays that can serve as an efficient complement to the time-consuming colony forming unit assay usually used in CLS studies.