PARP1 and phospho-p65 protein expression is increased in human HER2-positive breast cancers

Previous studies have shown that basal breast cancers, which may have an inherent “BRCAness” phenotype and sensitivity to inhibitors of poly (ADP-Ribose) polymerase (PARP), express elevated levels of PARP1. Our lab recently reported that HER2+ breast cancers also exhibit sensitivity to PARP inhibito...

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Veröffentlicht in:Breast cancer research and treatment 2015-04, Vol.150 (3), p.569-579
Hauptverfasser: Stanley, Jennifer, Klepczyk, Lisa, Keene, Kimberly, Wei, Shi, Li, Yufeng, Forero, Andres, Grizzle, William, Wielgos, Monica, Brazelton, Jason, LoBuglio, Albert F., Yang, Eddy S.
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Sprache:eng
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Zusammenfassung:Previous studies have shown that basal breast cancers, which may have an inherent “BRCAness” phenotype and sensitivity to inhibitors of poly (ADP-Ribose) polymerase (PARP), express elevated levels of PARP1. Our lab recently reported that HER2+ breast cancers also exhibit sensitivity to PARP inhibitors (PARPi) by attenuating the NF-κB pathway. In this study, we assessed PARP1 and phospho-p65, a marker of activated NF-κB levels in human breast cancer tissues. PARP1 and PARP2 copy number, mRNA, and protein expression was assessed by interrogating the PAM-50 defined breast cancer patient set from the TCGA using cBioPortal. PARP1 and phospho-p65 immunohistochemistry and correlation to clinical parameters was conducted using 307 primary breast cancer specimens (132 basal, 82 luminal, 93 HER2+) through univariate and multivariate analyses. In the PAM50 breast cancer data set, PARP1 and 2 expression was altered in 24/58 (41 %) HER2+, 32/81 (40 %) basal, and 75/324 (23 %) luminal A/B breast cancer patients. This correlated with a statistically significant increase in PARP1 protein levels in HER2+ and basal but not luminal breast cancers ( p  = 0.003, p  = 0.027, p  = 0.289, respectively). No change in PARP2 protein level was observed. Interestingly, using breast cancer specimens from 307 patients, HER2 positivity correlated with elevated PARP1 expression ( p  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-015-3359-6