We found that the oncogene Multiple Copies in T-cell Malignancy 1 (MCT-1/MCTS1) expression is a new poor-prognosis marker in patients with aggressive breast cancers.
High expression of MCT1 and MCT4 in tumour tissues was associated with poor patient outcome; further the correlation between MCT1 expression and poor prognosis in breast cancer was further strengthened when combined with MCT4 overexpression in the adjacent adipose tissue.
In the present study, we show that proton-driven lactate flux is enhanced by the intracellular carbonic anhydrase CAII, which is colocalized with the monocarboxylate transporter MCT1 in MCF-7 breast cancer cells.
Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer.
Therefore, we assayed for the expression levels and the localizations of MCT (1, 2, and 4), and LDH (A and B) isoforms in breast cancer cell lines MCF-7 and MDA-MB-231 and compared results with those from a control, untransformed primary breast cell line, HMEC 184.
Taken together, our results suggest that MCT-1 may contribute to the pathogenesis and progression of human breast cancer via at least two routes: promotion of angiogenesis through the decline of TSP1 and inhibition of apoptosis.