Ehsan Sohrabi1, Masoumeh Moslemi1, Ehsan Rezaie2, Nahid Nafissi3, Mansoor Khaledi4, Hamed Afkhami4, Javad Fathi5, Ali Zekri6. 1. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran. 2. Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Science, Tehran, Iran. 3. Department of Surgery, Breast Department of Rasool Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran. Nafissi.n@iums.ac.ir. 4. Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran. 5. Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran. h.a.university.ac@gmail.com.
Abstract
BACKGROUND: Breast cancer (BC) is a common malignancy with a high mortality rate. Malignant cell transformation is associated with metabolic changes. One group of proteins that are affected is the monocarboxylate transporters (MCTs-SLC16A). The MCTs comprise 14 members, and they play an important role in the growth, proliferation, and metabolism of cancer cells by transporting monocarboxylates such as lactate, pyruvate and thyroid hormones. OBJECTIVE: We aimed to evaluate the expression of MCT3 (SLC16A8), MCT8 (SLC16A2) and MCT9 (SLC16A9) genes in breast cancer samples, comparing to normal adjacent tissues. METHODS: Forty paired breast cancer tumor samples, the adjacent non-tumor and five healthy tissues were collected. Three cancer cell lines (MCF-7, MDA-MB-231, and SKBR3) were also analyzed. The expression of SLC16A8, SLC16A2 and SLC16A9 were assessed using quantitative real-time PCR. The relationship between gene expression with the pathological features of the tumors, and the hormone receptors status of the patient's tumors were also analyzed. RESULTS: There was a significantly lower expression of the MCT3 gene in tumor samples compared to adjacent normal tissue and healthy samples (p value < 0.05). There was a significant difference in the expression of all three candidate genes between the BC tissues and normal tissues, and for the, tissues with different hormone receptor status and the molecular subtypes. Altered MCT8 and MCT9 gene expression was associated with a reduced survival CONCLUSION: MCT3 expression is significantly downregulated in breast cancer tissue. MCT3 may represent a novel therapeutic target in breast cancer patients, or in some hormone receptor subgroups.
BACKGROUND: Breast cancer (BC) is a common malignancy with a high mortality rate. Malignant cell transformation is associated with metabolic changes. One group of proteins that are affected is the monocarboxylate transporters (MCTs-SLC16A). The MCTs comprise 14 members, and they play an important role in the growth, proliferation, and metabolism of cancer cells by transporting monocarboxylates such as lactate, pyruvate and thyroid hormones. OBJECTIVE: We aimed to evaluate the expression of MCT3 (SLC16A8), MCT8 (SLC16A2) and MCT9 (SLC16A9) genes in breast cancer samples, comparing to normal adjacent tissues. METHODS: Forty paired breast cancer tumor samples, the adjacent non-tumor and five healthy tissues were collected. Three cancer cell lines (MCF-7, MDA-MB-231, and SKBR3) were also analyzed. The expression of SLC16A8, SLC16A2 and SLC16A9 were assessed using quantitative real-time PCR. The relationship between gene expression with the pathological features of the tumors, and the hormone receptors status of the patient's tumors were also analyzed. RESULTS: There was a significantly lower expression of the MCT3 gene in tumor samples compared to adjacent normal tissue and healthy samples (p value < 0.05). There was a significant difference in the expression of all three candidate genes between the BC tissues and normal tissues, and for the, tissues with different hormone receptor status and the molecular subtypes. Altered MCT8 and MCT9 gene expression was associated with a reduced survival CONCLUSION: MCT3 expression is significantly downregulated in breast cancer tissue. MCT3 may represent a novel therapeutic target in breast cancer patients, or in some hormone receptor subgroups.
Authors: Julia Badziong; Saskia Ting; Sarah Synoracki; Vera Tiedje; Klaudia Brix; Georg Brabant; Lars Christian Moeller; Kurt Werner Schmid; Dagmar Fuhrer; Denise Zwanziger Journal: Eur J Endocrinol Date: 2017-06-02 Impact factor: 6.664
Authors: Edith C H Friesema; Sumita Ganguly; Amal Abdalla; Jocelyn E Manning Fox; Andrew P Halestrap; Theo J Visser Journal: J Biol Chem Date: 2003-07-18 Impact factor: 5.157
Authors: Darshan S Chandrashekar; Bhuwan Bashel; Sai Akshaya Hodigere Balasubramanya; Chad J Creighton; Israel Ponce-Rodriguez; Balabhadrapatruni V S K Chakravarthi; Sooryanarayana Varambally Journal: Neoplasia Date: 2017-07-18 Impact factor: 5.715