Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress

Scientific Reports
Cheng-Yu LinPascal H G Duijf

Abstract

Encoded by EEF1A1, the eukaryotic translation elongation factor eEF1α1 strongly promotes the heat shock response, which protects cancer cells from proteotoxic stress, following for instance oxidative stress, hypoxia or aneuploidy. Unexpectedly, therefore, we find that EEF1A1 mRNA levels are reduced in virtually all breast cancers, in particular in ductal carcinomas. Univariate and multivariate analyses indicate that EEF1A1 mRNA underexpression independently predicts poor patient prognosis for estrogen receptor-positive (ER+) cancers. EEF1A1 mRNA levels are lowest in the most invasive, lymph node-positive, advanced stage and postmenopausal tumors. In sharp contrast, immunohistochemistry on 100 ductal breast carcinomas revealed that at the protein level eEF1α1 is ubiquitously overexpressed, especially in ER+ , progesterone receptor-positive and lymph node-negative tumors. Explaining this paradox, we find that EEF1A1 mRNA levels in breast carcinomas are low due to EEF1A1 allelic copy number loss, found in 27% of tumors, and cell cycle-specific expression, because mRNA levels are high in G1 and low in proliferating cells. This also links estrogen-induced cell proliferation to clinical observations. In contrast, high eEF1α1 protein ...Continue Reading

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Citations

Feb 12, 2019·Journal of Cellular Physiology·Behzad MansooriBehzad Baradaran
Nov 11, 2019·Journal of Clinical Medicine·Eun Kyo JoungJi Hyung Hong
Sep 3, 2020·Chembiochem : a European Journal of Chemical Biology·Alejandra A CarrilesFederico Gago
Sep 21, 2021·Drug Delivery and Translational Research·Ahmad Reza FarmaniNima Rezaei

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Methods Mentioned

BETA
environmental stress
RNAseq
reverse-transcription PCR
exome sequencing
PCR

Software Mentioned

Adjuvant ! Online
METABRIC
Adjuvant
! Online

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