SLC37A1 gene expression is up-regulated by epidermal growth factor in breast cancer cells.
Phospholipid biosynthesis exerts an important role in the proliferation of tumor cells; however, the regulation of the proteins involved in this context still remains to be fully evaluated. SLC37A1 protein belongs to a small family of sugar-phosphate/phosphate exchangers. The sequence homology with the bacterial glycerol-3-phosphate transporter (30%) suggests that SLC37A1 might be able to catalyze an exchange of glycerol-3-phosphate against phosphate. Glycerol-3-phosphate, found in different cellular compartments, is a fundamental substrate in phospholipid biosynthesis. In the present study, we demonstrate for the first time that epidermal growth factor (EGF) transactivates SLC37A1 promoter sequence and induces SLC37A1 mRNA, and protein expression through the EGFR/MAPK/Fos transduction pathway in ER-negative SkBr3 breast cancer cells. These findings were corroborated by comparable results obtained in ER-positive endometrial Ishikawa tumor cells. Interestingly, we also show that SLC37A1 protein localizes in the endoplasmic reticulum, hence supporting its possible involvement in phospholipid biosynthesis. On the basis of our data, the up-regulation of SLC37A1 gene expression should be included among the well-known stimulatory action exerted by EGF in breast cancer cells. In addition, further studies are required to provide evidence concerning the potential role of EGF-mediated SLC37A1 induction in breast tumor cells.
Iacopetta
Domenico
D
Department of Pharmaco-Biology, University of Calabria, 87036 Rende (CS), Italy.
Lappano
Rosamaria
R
Cappello
Anna Rita
AR
Madeo
Marianna
M
De Francesco
Ernestina Marianna
EM
Santoro
Antonella
A
Curcio
Rosita
R
Capobianco
Loredana
L
Pezzi
Vincenzo
V
Maggiolini
Marcello
M
Dolce
Vincenza
V
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; C036527:SLC37A1 protein, human; D008156:Luciferases; C512478:EGFR protein, human; D066246:ErbB Receptors