Variations in the mRNA expression of poly(ADP‐ribose) polymerases, poly(ADP‐ribose) glycohydrolase and ADP‐ribosylhydrolase 3 in breast tumors and impact on clinical outcome. Issue 12 (9th August 2013)

• Record Type: Journal Article
• Authors: Bieche, Ivan; Pennaneach, Vincent; Driouch, Keltouma; Vacher, Sophie; Zaremba, Tomasz; Susini, Aurélie; Lidereau, Rosette; Hall, Janet
• Is Part Of: International journal of cancer. Volume 133:Issue 12(2013:Dec. 15)
• Page Start: 2791
• Page End: 2800
• Publication Date: 2013-08-09
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28304
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In order to assess the variation in expression of poly(ADP‐ribose) polymerase (PARP) family members and the hydrolases that degrade the poly(ADP‐ribose) polymers they generate and possible associations with classical pathological parameters, including long‐term outcome, the mRNA levels of <italic>PARP1</italic>, <italic>PARP2</italic>, <italic>PARP3</italic>, <italic>poly(ADP‐ribose) glycohydrolase (PARG)</italic> and <italic>ADP‐ribosylhydrolase 3 (ARH3)</italic> were examined using quantitative reverse transcription polymerase chain reaction in 443 unilateral invasive breast cancers and linked to hormonal status, tumor proliferation and clinical outcome. <italic>PARP1</italic> mRNA levels were the highest among these five genes in both normal and tumor tissues, with a 2.45‐fold higher median level in tumors compared to normal tissues. Tumors (34.1%) showed <italic>PARP1</italic> overexpression (>3 fold relative to normal breast tissues) compared to underexpression (<0.33 fold) in only 0.5%. This overexpression was seen in all breast tumor subgroups, with the highest fraction (51%) seen in the HR‐positive/ERBB2‐positive subgroup and was not highly associated with any other classical predictive factors. No correlation was seen between <italic>PARP1</italic> mRNA and PARP‐1 protein levels in a subset of 31 tumors. <italic>PARP3</italic> was underexpressed in 10.4% of tumors, more frequently in the HR‐negative tumors (25.4%) than the HR‐positive tumors (5.9%). This <italic>PARP3</italic> underexpression was mutually exclusive with a <italic>PARP1</italic> overexpression. <italic>PARP2</italic> levels were unchanged between normal and tumor tissues and few tumors showed overexpression of <italic>PARG</italic> (3.8%) or <italic>ARH3</italic> (3.4%). Within the subgroup of triple negative tumors, <italic>PARG</italic> mRNA levels below the median were associated with a higher risk of developing metastases (<italic>p</italic> = 0.039) raising the possibility this might be marker of clinical outcome.</p> </abstract>