HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Transcriptional up-regulation of PHLDA1 by 17beta-estradiol in MCF-7 breast cancer cells.

Abstract
Most breast cancer risk factors are associated with prolonged exposure of the mammary gland to high levels of estrogens. The actions of estrogens are predominantly mediated by two receptors, ERalpha and ERbeta, which act as transcription factors binding with high affinity to estrogen response elements in the promoter region of target genes. However, most target genes do not contain the consensus estrogen response elements, but rather degenerated palindromic sequences showing one or more mutations and other ER-binding sites such as AP-1 and SP-1. Using the differential display reverse transcription-polymerase chain reaction technique, our group identified several genes differentially expressed in normal tissue and in ER-positive and ER-negative primary breast tumors. One of the genes shown to be down-regulated in breast tumors compared to normal breast tissue was the PHLDA1 (Pleckstrin homology-like domain, family A, member 1). In the present study, we investigated the potential of PHLDA1 to be regulated by estrogen via ER in MCF-7 breast cancer cells. The promoter region of PHLDA1 shows an imperfect palindrome, an AP-1- and three SP-1-binding sites potentially regulated by estrogens. We also assessed the effects of 17beta-estradiol on PHLDA1 mRNA expression in MCF-7 breast cancer cells. MCF-7 cells exposed to 10 nM 17beta-estradiol showed more than 2-fold increased expression of the PHLDA1 transcripts compared to control cells (P = 0.05). The anti-estrogen ICI 182,780 (1 microM) inhibited PHLDA1 mRNA expression and completely abolished the effect of 10 nM 17beta-estradiol on PHLDA1 expression (P < 0.05), suggesting that PHLDA1 is regulated by estrogen via ER.
AuthorsA C Marchiori, D A Casolari, M A Nagai
JournalBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 41 Issue 7 Pg. 579-82 (Jul 2008) ISSN: 1414-431X [Electronic] Brazil
PMID18641796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • PHLDA1 protein, human
  • RNA, Messenger
  • Receptors, Estrogen
  • Transcription Factors
  • Estradiol
Topics
  • Breast Neoplasms (genetics, metabolism)
  • Cell Line, Tumor (drug effects)
  • Estradiol (pharmacology)
  • Female
  • Gene Expression Regulation, Neoplastic (drug effects, genetics)
  • Humans
  • RNA, Messenger (genetics, metabolism)
  • Receptors, Estrogen (metabolism)
  • Transcription Factors (drug effects, genetics)
  • Transcription, Genetic (drug effects)
  • Up-Regulation

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: