当前位置： SCI文献检索 > BREAST CANCER RESEARCH期刊下所有文献 > ELF5 isoform expression is tissue-specific and significantly altered in cancer.

ELF5 isoform expression is tissue-specific and significantly altered in cancer.

Abstract：

BACKGROUND:E74-like factor 5 (ELF5) is an epithelial-specific member of the E26 transforming sequence (ETS) transcription factor family and a critical regulator of cell fate in the placenta, pulmonary bronchi, and milk-producing alveoli of the mammary gland. ELF5 also plays key roles in malignancy, particularly in basal-like and endocrine-resistant forms of breast cancer. Almost all genes undergo alternative transcription or splicing, which increases the diversity of protein structure and function. Although ELF5 has multiple isoforms, this has not been considered in previous studies of ELF5 function. METHODS:RNA-sequencing data for 6757 samples from The Cancer Genome Atlas were analyzed to characterize ELF5 isoform expression in multiple normal tissues and cancers. Extensive in vitro analysis of ELF5 isoforms, including a 116-gene quantitative polymerase chain reaction panel, was performed in breast cancer cell lines. RESULTS:ELF5 isoform expression was found to be tissue-specific due to alternative promoter use but altered in multiple cancer types. The normal breast expressed one main isoform, while in breast cancer there were subtype-specific alterations in expression. Expression of other ETS factors was also significantly altered in breast cancer, with the basal-like subtype demonstrating a distinct ETS expression profile. In vitro inducible expression of the full-length isoforms 1 and 2, as well as isoform 3 (lacking the Pointed domain) had similar phenotypic and transcriptional effects. CONCLUSIONS:Alternative promoter use, conferring differential regulatory responses, is the main mechanism governing ELF5 action rather than differential transcriptional activity of the isoforms. This understanding of expression and function at the isoform level is a vital first step in realizing the potential of transcription factors such as ELF5 as prognostic markers or therapeutic targets in cancer.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Piggin CL,Roden DL,Gallego-Ortega D,Lee HJ,Oakes SR,Ormandy CJ

doi

10.1186/s13058-015-0666-0

subject

Has Abstract

pub_date

2016-01-07 00:00:00

pages

issue

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-015-0666-0

journal_volume

pub_type

杂志文章

在线工具

ELF5 isoform expression is tissue-specific and significantly altered in cancer.