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PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast

J M Gozgit1, B T Pentecost, S A Marconi

  • 1Department of Veterinary and Animal Sciences, University of Massachusetts, Morrill 1 North, Amherst, MA 01003-9298, USA.

British Journal of Cancer
|August 30, 2007
PubMed

Insights

This study reveals phospholipase D1 (PLD1) is upregulated in a novel breast cancer cell line and in human tumors expressing basal cytokeratins. PLD1 and phospho-mammalian target of rapamycin (mTOR) are coexpressed in some phospho-Akt-negative breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The human oestrogen receptor (ER)-positive MCF-7 cell line variant, TMX2-28, lacks ER expression and exhibits basal cytokeratins (CKs) 5, 14, and 17.
  • Microarray analysis revealed significant transcriptomic differences between TMX2-28 and MCF-7 cells, identifying phospholipase D1 (PLD1) as a key differentially expressed gene.

Purpose of the Study:

  • To investigate the expression and potential role of phospholipase D1 (PLD1) in breast cancer.
  • To correlate PLD1 expression with specific breast cancer subtypes and signaling pathways.

Main Methods:

  • Utilized a novel ER-negative breast cancer cell line model (TMX2-28).
  • Employed cDNA microarray and real-time RT-PCR to quantify PLD1 mRNA levels.
  • Performed immunohistochemistry (IHC) to assess PLD1, CK5/17, phospho-Akt, and phospho-mammalian target of rapamycin (mTOR) protein expression in human breast tumors.

Main Results:

  • PLD1 mRNA was 10-fold higher in TMX2-28 cells compared to MCF-7 cells.
  • PLD1 mRNA levels correlated with high basal CK5 and/or CK17 expression in breast tumors.
  • PLD1 protein overexpression was observed in 24% of breast tumors, notably in those with high CK5/17 expression.
  • PLD1 and phospho-mTOR were coexpressed in a subset of phospho-Akt-negative breast carcinomas.

Conclusions:

  • Phospholipase D1 (PLD1) is a potential biomarker for basal-like features in breast cancer.
  • The coexpression of PLD1 and phospho-mammalian target of rapamycin (mTOR) in phospho-Akt-negative breast cancers suggests a distinct signaling pathway in a subset of these tumors.

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