MAP17 and SGLT1 protein expression levels as prognostic markers for cervical tumor patient survival.

Abstract

MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS) generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types.

• Authors: Marco Perez, Juan M Praena-Fernandez, Blanca Felipe-Abrio, Maria A Lopez-Garcia, Antonio Lucena-Cacace, Angel Garcia, Matilde Lleonart, Guiovanna Roncador, Juan J Marin, Amancio Carnero
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e56169 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23418532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Membrane Proteins
• PDZK1IP1 protein, human
• Reactive Oxygen Species
• SLC5A1 protein, human
• Sodium-Glucose Transporter 1
• Glucose
• Cisplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage)
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Cell Survival (drug effects)
• Chemoradiotherapy
• Cisplatin (administration & dosage)
• Female
• Gene Expression Regulation, Neoplastic
• Glucose (metabolism, pharmacokinetics)
• HeLa Cells
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Membrane Proteins (genetics, metabolism)
• Middle Aged
• Prognosis
• Reactive Oxygen Species (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium-Glucose Transporter 1 (genetics, metabolism)
• Treatment Outcome
• Uterine Cervical Neoplasms (genetics, metabolism, therapy)