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Identification of novel epigenetically inactivated gene PAMR1 in breast carcinoma

Paulisally Hau Yi Lo1, Chizu Tanikawa1, Toyomasa Katagiri2

  • 1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Oncology Reports
|November 6, 2014
PubMed

Insights

Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is suppressed in breast cancer due to promoter hypermethylation. Restoring PAMR1 expression inhibited cancer cell growth, identifying it as a potential tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Cancer development involves genetic and epigenetic changes.
  • Peptidase domain containing associated with muscle regeneration 1 (PAMR1) role in breast cancer is largely unknown.

Purpose of the Study:

  • To investigate the role of PAMR1 in breast cancer.
  • To determine the mechanism of PAMR1 regulation in breast cancer.

Main Methods:

  • Microarray analysis of 81 breast carcinoma specimens.
  • DNA sequencing of the PAMR1 promoter.
  • Treatment with 5-aza-2' deoxycytidine.
  • Ectopic expression of PAMR1 in cancer cells.

Main Results:

  • PAMR1 was frequently suppressed in breast cancer tissues and cell lines.
  • PAMR1 promoter was hypermethylated in breast cancer specimens.
  • 5-aza-2' deoxycytidine treatment restored PAMR1 expression.
  • Ectopic PAMR1 expression suppressed cancer cell growth.

Conclusions:

  • PAMR1 acts as a tumor suppressor in breast cancer.
  • Promoter hypermethylation is a key mechanism for PAMR1 inactivation.
  • PAMR1 is a potential therapeutic target for breast cancer.

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