The tissue expression of MCT3, MCT8, and MCT9 genes in women with breast cancer

Genes Genomics. 2021 Sep;43(9):1065-1077. doi: 10.1007/s13258-021-01116-w. Epub 2021 Jun 7.

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.

Keywords: Breast cancer; Cancer metabolism; Lactate dehydrogenase; Monocarboxylate transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • L-Lactate Dehydrogenase / genetics
  • Lactic Acid / metabolism
  • MCF-7 Cells
  • Middle Aged
  • Monocarboxylic Acid Transporters / genetics*
  • Symporters / genetics*

Substances

  • Monocarboxylic Acid Transporters
  • SLC16A2 protein, human
  • SLC16A3 protein, human
  • SLC16A9 protein, human
  • Symporters
  • Lactic Acid
  • L-Lactate Dehydrogenase