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Sp1 is necessary for gene activation of Adamts17 by estrogen

Zanhui Jia1, Shuping Gao, Nadira M'Rabet

  • 1Clinic of Gynecological Endocrinology and Reproductive Medicine, University of Basel, Spitalstrasse 21, CH-4031, Basel, Switzerland; Department of Biomedicine, University of Basel, Hebelstrasse 20, CH-4031, Basel, Switzerland; Department of Gynecology and Obstetrics, Second Hospital of Jilin University, Changchun City, Jilin Province, P.R. China.

Journal of Cellular Biochemistry
|June 7, 2014
PubMed

Insights

Adamts17 (ADAM metallopeptidase domain 17) knockdown inhibits breast cancer growth and induces apoptosis. Estrogen rapidly induces Adamts17, regulated by Sp1 and epigenetic factors, suggesting Adamts17 promotes cancer survival.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Adamts17 (ADAM metallopeptidase domain 17) is a secreted metalloproteinase.
  • Its role in cancer, particularly breast cancer, is not fully understood.

Purpose of the Study:

  • To investigate the function of Adamts17 in breast cancer cell growth and survival.
  • To elucidate the regulatory mechanisms of Adamts17 gene expression.

Main Methods:

  • siRNA knockdown of Adamts17, Sp1, and Myc in breast cancer cells.
  • Reporter assays to analyze promoter activity.
  • Treatment with histone deacetylase (HDAC) and methylase inhibitors.
  • Meta-analysis of Oncomine microarray data.

Main Results:

  • Knockdown of Adamts17 inhibited breast cancer cell growth and induced apoptosis.
  • Estrogen rapidly induced Adamts17 expression, dependent on Sp1 transcription factor.
  • Sp1 binding elements may be located in intronic regions, contributing to estrogen responsiveness.
  • Sp1 and Myc binding in the proximal promoter influenced basal Adamts17 expression.
  • HDAC and methylase inhibitors increased Adamts17 expression, suggesting epigenetic regulation.
  • Higher Adamts17 expression was observed in human breast ductal carcinoma subtypes.
  • Elevated Adamts17 expression correlated inversely with patient survival.

Conclusions:

  • Adamts17 plays a role in promoting breast cancer cell growth and survival.
  • Adamts17 expression is regulated by estrogen, Sp1, and epigenetic modifications.
  • Adamts17 represents a potential therapeutic target for breast cancer.
Keywords:
APOPTOSISAdamts17BREAST CANCERGENE REGULATIONSp1

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