PMID- 17726467 OWN - NLM STAT- MEDLINE DCOM- 20071019 LR - 20220318 IS - 0007-0920 (Print) IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 97 IP - 6 DP - 2007 Sep 17 TI - PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas. PG - 809-17 AB - We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT-PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas. FAU - Gozgit, J M AU - Gozgit JM AD - Department of Veterinary and Animal Sciences, University of Massachusetts, Morrill 1 North, Amherst, MA 01003-9298, USA. FAU - Pentecost, B T AU - Pentecost BT FAU - Marconi, S A AU - Marconi SA FAU - Ricketts-Loriaux, R S J AU - Ricketts-Loriaux RS FAU - Otis, C N AU - Otis CN FAU - Arcaro, K F AU - Arcaro KF LA - eng GR - R01 ES009795/ES/NIEHS NIH HHS/United States GR - K02 ES000384/ES/NIEHS NIH HHS/United States GR - R01 ES09795/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070828 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (DNA, Complementary) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Estrogen) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.1.4.4 (phospholipase D1) SB - IM MH - Blotting, Western MH - Breast Neoplasms/*enzymology/metabolism MH - Cell Line, Tumor MH - DNA, Complementary/metabolism MH - Female MH - Humans MH - Immunohistochemistry MH - Microarray Analysis MH - Oncogene Protein v-akt/metabolism MH - Phospholipase D/genetics/*metabolism MH - Protein Kinases/*metabolism MH - RNA, Messenger/metabolism MH - Receptors, Estrogen/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - TOR Serine-Threonine Kinases MH - Up-Regulation PMC - PMC2360386 EDAT- 2007/08/30 09:00 MHDA- 2007/10/20 09:00 PMCR- 2008/09/11 CRDT- 2007/08/30 09:00 PHST- 2007/08/30 09:00 [pubmed] PHST- 2007/10/20 09:00 [medline] PHST- 2007/08/30 09:00 [entrez] PHST- 2008/09/11 00:00 [pmc-release] AID - 6603926 [pii] AID - 10.1038/sj.bjc.6603926 [doi] PST - ppublish SO - Br J Cancer. 2007 Sep 17;97(6):809-17. doi: 10.1038/sj.bjc.6603926. Epub 2007 Aug 28.