KlRox1p contributes to yeast resistance to metals and is necessary for KlYCF1 expression in the presence of cadmium.

We have characterized the KlROX1 gene from Kluyveromyces lactis and verified that it does not regulate the hypoxic response in this yeast, oppositely to the Saccharomyces cerevisiae homologue ScROX1. The KlROX1 promoter is not regulated by KlHap1p or KlRox1p in response to changes aerobiosis/hypoxia. Besides, KlRox1p expression only partially represses ScANB1 in S. cerevisiae and does not regulate the ScANB1 and KlHEM13 promoters in K. lactis. KlRox1p does not interact either with KlTup1p or KlSsn6p or with their homologues ScTup1p and ScSsn6p, which are components of the general co-repressor factor that mediates the transcriptional repression exerted by ScRox1p in S. cerevisiae. We have found that KlROX1 mediates the response to arsenate and cadmium and, in the presence of cadmium, it is necessary for KlYCF1 expression, a gene encoding a protein with homology to the yeast cadmium and arsenite vacuolar transporter. EMSA assays show that KlRox1p binds, through its HMG domain, to a DNA sequence present in the KlYCF1 promoter. Although in S. cerevisiae the function of ScRox1p in cadmium resistance was already known and linked to regulation of ScFET4 expression, we have found that ScRox1p also regulates ScYCF1transcription and binds to its promoter.

Potential role of sugar transporters in cancer and their relationship with anticancer therapy.

Sugars, primarily glucose and fructose, are the main energy source of cells. Because of their hydrophilic nature, cells use a number of transporter proteins to introduce sugars through their plasma membrane. Cancer cells are well known to display an enhanced sugar uptake and consumption. In fact, sugar transporters are deregulated in cancer cells so they incorporate higher amounts of sugar than normal cells. In this paper, we compile the most significant data available about biochemical and biological properties of sugar transporters in normal tissues and we review the available information about sugar carrier expression in different types of cancer. Moreover, we describe the possible pharmacological interactions between drugs currently used in anticancer therapy and the expression or function of facilitative sugar transporters. Finally, we also go into the insights about the future design of drugs targeted against sugar utilization in cancer cells.

Glucose transporter expression and the potential role of fructose in renal cell carcinoma: A correlation with pathological parameters.

All mammalian cells contain one or more members of the facilitative glucose transporter (GLUT) gene family. Glucose transporter membrane proteins (GLUT) regulate the movement of glucose between the extracellular and intracellular compartments, maintaining a constant supply of glucose available for metabolism. Tumor cells are highly energy-dependent, therefore GLUT overexpression is often observed. In fact, overexpression of GLUT1 has been correlated with hypoxia markers in several tumor types, including renal cell carcinoma (RCC). We retrospectively analyzed 80 paraffin-embedded RCC samples. The pattern of GLUT1-5 expression in RCC specimens was evaluated using tissue-array technology and correlated with histological tumor characteristics. Pathological parameters included tumor location, renal pelvis, vein and lymph vessel invasion, capsule breakage, histological subtype, Furhman grade, hilar invasion and tumor stage at diagnosis. The expression of five facilitative glucose transporters, GLUT1 (erythrocyte type), GLUT2 (liver type), GLUT3 (brain type), GLUT4 (muscle/fat type) and GLUT5 (small intestinal type), was semi-quantitatively analyzed. In non-parametric, Mann-Whitney U and Kruskal-Wallis tests, a significant positive correlation was consistently found between moderately differentiated RCC tissues and the expression of GLUT5 (p=0.024). Patients who had pelvic invasion and capsule breakage at diagnosis also showed increased GLUT5 expression levels (p=0.039 and p=0.019, respectively). Moreover, GLUT5 showed statistical significance in those samples identified as being of clear cell histological type (p=0.001). A high expression of GLUT5 in human RCC was observed. GLUT5 appears to be correlated with grade II differentiation, locoregional invasion and aggressiveness, and may play a role in RCC development.