Aberrant overexpression of membrane-associated mucin contributes to tumor progression in adult T-cell leukemia/lymphoma cells

Abstract

Aberrant overexpression of membrane-associated mucin (MUC1) is implicated in the pathogenesis of cancer, particularly of adenocarcinomas. Adult T-cell leukemia/lymphoma (ATL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), exhibits invasive tropism into various organs, resulting in disease progression and resistance to treatment. In the present study, we showed that MUC1 is overexpressed exclusively in cells of ATL among hematological malignancies. Furthermore, increased expression of MUC1 correlated with a poor prognosis, suggesting MUC1 to be a prognostic marker in ATL. Various functional analyses with knockdown experiments using a specific siRNA for MUC1 revealed that MUC1 is involved in cell growth, cell aggregation, and resistance to apoptosis. Although it has been shown that the anti-adhesive properties of MUC1 facilitate migration and metastasis of tumor cells, our findings indicated that MUC1 contributes to cell–cell adhesion. Mucins thus seem to play a role in the pathogenesis and/or progression of ATL.

Keywords:

• MUC1
• adult T-cell leukemia/lymphoma
• adhesion molecules
• apoptosis

Acknowledgement

This study was supported in part by a Grant-in-Aid for Scientific Research (20590580) and a Grant-in Aid for Exploratory Research (21659149) from the Japan Society for the Promotion of Science.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal .