Altered SERCA Expression in Breast Cancer.

Panayiota Christodoulou,Andreas Yiallouris,Ioannis Patrikios,Maria-Ioanna Christodoulou,Panagiotis K Politis,Artemis Michail

doi:10.3390/medicina57101074

Abstract

Background and Objectives: Calcium (Ca2+) signaling is critical for the normal functioning of various cellular activities. However, abnormal changes in cellular Ca2+ can contribute to pathological conditions, including various types of cancer. The maintenance of intracellular Ca2+ levels is achieved through tightly regulated processes that help maintain Ca2+ homeostasis. Several types of regulatory proteins are involved in controlling intracellular Ca2+ levels, including the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA), which maintains Ca2+ levels released from the SR/ER. In total, three ATPase SR/ER Ca2+-transporting (ATP2A) 1-3 genes exist, which encode for several isoforms whose expression profiles are tissue-specific. Recently, it has become clear that abnormal SERCA expression and activity are associated with various types of cancer, including breast cancer. Breast carcinomas represent 40% of all cancer types that affect women, with a wide variety of pathological and clinical conditions. Materials and methods: Using cBioPortal breast cancer patient data, Kaplan–Meier plots demonstrated that high ATP2A1 and ATP2A3 expression was associated with reduced patient survival. Results: The present study found significantly different SERCA specific-type expressions in a series of breast cancer cell lines. Moreover, bioinformatics analysis indicated that ATP2A1 and ATP2A3 expression was highly altered in patients with breast cancer. Conclusion: Overall, the present data suggest that SERCA gene-specific expressioncan possibly be considered as a crucial target for the control of breast cancer development and progression.

Highlights

Intracellular calcium ion (Ca2+ ) signaling [1] pathways are involved in key cellular processes, including excitation–contraction coupling, stimulus–secretion coupling, gene expression, control of the cell cycle, cell motility, autophagy, and apoptosis [2,3,4]
To determine the expression levels of SERCA-A1, A2, and A3 in breast cancer cells, the present study examined the protein expression profiles in MCF-7, MDA 231, and T47D
These findings suggested a differential expression profile of SERCA-A1-3 in various subtypes of breast cancer cell lines

Summary

Introduction

Intracellular calcium ion (Ca2+ ) signaling [1] pathways are involved in key cellular processes, including excitation–contraction coupling, stimulus–secretion coupling, gene expression, control of the cell cycle, cell motility, autophagy, and apoptosis [2,3,4]. There are three SERCA ATPase SR/ER Ca2+ -transporting (ATP2A) eukaryotic genes that exist, which encode for 14 isoforms with tissue-specific expression profiles [7,8,9,10]. SERCA3 can be transcribed to three isoforms, SERCA3a–3c, all expressed in non-muscle cells [13]. Several studies have reported alterations in SERCA gene-specific expression in various types of cancer, suggesting that levels of SERCA may be potential therapeutic targets and biomarkers in cancer [1]

Methods

Results

Conclusion