Estrogenic regulation of cholesterol biosynthesis and cell growth in DLD-1 human colon cancer cells

Caterina Messa, Maria Notarnicola, Francesco Russo, Aldo Cavallini, Valentina Pallottini, Anna Trentalance, Maurizio Bifulco, Chiara Laezza, Maria Gabriella Caruso

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. The main molecules of cholesterol homeostasis are 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), the key enzyme of the biosynthetic pathway, and the low-density lipoprotein receptor (LDL-R), which is responsible for the uptake of plasma lipoproteins. The increase in the endogenous cholesterol biosynthesis results in stimulation of DNA synthesis, while the inhibition of cholesterogenesis suppresses cell growth. Estrogens have been reported to regulate hepatic LDL-R expression and modulate cell proliferation in different tissues. In order to clarify the mechanisms of estrogenic growth control in colorectal carcinoma, we have investigated the effects of 17β-estradiol exposure on LDL-R gene expression and its protein, as well as on HMG-CoAR gene expression, its protein as well as enzyme activity in the DLD-1 human colon cancer cell line. The effect of 17β-estradiol on both cell growth and apoptosis in this cell line was also investigated. Material and methods. LDL-R and HMG-CoAR gene expressions were determined using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in DLD-1 cells at different times and doses of 17β-estradiol exposure. LDL-R and HMG-CoAR protein expression was detected by Western immunoblotting. HMG-CoAR activity was evaluated using a radiometric assay. Cell proliferation was measured by colorimetric MTT test and incorporation of [3H]-thymidine in DNA. Apoptotic death was estimated by DNA fragmentation analysis. Results. Estrogens induced an early increase of LDL-R, at both mRNA and protein level, and later decreased HMG-CoAR activity and protein expression. DLD-1 cells treated with 17β-estradiol exhibited inhibition of DNA synthesis and apoptosis. Conclusions. The results of this study suggest that estrogens regulate LDL-R and HMG-CoAR and influence cell growth and apoptosis in colon cancer cells.

Original languageEnglish
Pages (from-to)1454-1461
Number of pages8
JournalScandinavian Journal of Gastroenterology
Volume40
Issue number12
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Apoptosis
  • Cell growth
  • Colon cancer
  • Estradiol
  • HMG-CoA reductase
  • LDL receptor

ASJC Scopus subject areas

  • Gastroenterology

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