Cancer Science & Therapy

SET domain-containing Protein 4 (SETD4) is a Newly Identified Cytosolic and Nuclear Lysine Methyltransferase involved in Breast Cancer Cell Proliferation

Abstract

Cancer is comprised of a multitude of epigenetic abnormalities, including the global loss and regional gain of
DNA methylation as well as alterations in histone methylation. Here, we characterize a new methyltransferase,
SET domain-containing protein 4 (SETD4), which is involved in breast carcinogenesis. Quantitative real-time PCR
(qPCR) showed elevated expression levels of SETD4 in several breast cancer cell lines. SETD4 overexpression
was confirmed by western blot analysis suggesting a correlation between high expression of SETD4 and a lack of
the estrogen receptor (ER) in breast cancer. In addition, cell fractionation studies and confocal immunofluorescence
revealed the nuclear and non-nuclear localization of this new protein. SETD4 knockdown in breast cancer cell lines
significantly suppressed their proliferation and delayed the G1/S cell cycle transition without affecting apoptosis.
Furthermore, western blot analysis showed that knockdown of SETD4 decreased cyclin D1 expression, revealing
the involvement of SETD4 in cell cycle regulation. These data imply that SETD4 plays a crucial role in breast
carcinogenesis and could be a novel molecular target for the development of new strategies for the diagnosis and
treatment of breast cancer.