Abstract 1843: Overexpression of polyisoprenylated methylated protein methyl esterase in triple negative breast cancer

Abstract

Abstract Lack of targeted, more effective therapies for triple negative breast cancer (TNBC) has necessitated the continuous search for protein biomarkers and targets for novel therapeutic development. Polyisoprenylated monomeric G-proteins such as Ras and Rab are hyperactive in about 30% of cancers and have profound effects on cell growth. Inhibition of polyisoprenylated methylated protein methyl esterase (PMPMEase) causes the death of cancer cells thus suggesting that hyperactivity of PMPMEase may result in cancers. The current studies were to address the hypothesis that PMPMEase activity is elevated in breast cancer. PMPMEase activity was determined in breast tumors and normal adjacent tissues (NAT) in snap-frozen tissues from 10 breast cancer cases. Five- to over 20-fold increases in PMPMEase activity compared to the respective NATs were detected in 8 of the 10 cases. Specific activities ranging from 0.25 ± 0.02 to 1.58 ± 0.07 nmol/h/mg were detected in the tumors compared to 0.09 nmol/h/mg or less in the NATs. Breast cancer tissue microarrays (TMAs) consisting of 125 independent breast cancer cases and NATs were analyzed for PMPMEase expression by immunohistochemistry and scored for their immunoreactive staining intensities. Intermediate to very strong immunoreactivities were detected in the breast cancer TMA core slices compared to only trace staining in those of the NATs. The mean scores ± SEM ranged from 310 ± 21, 290 ± 7, 350 ± 15, 360 ± 18, 390 ± 14, 360 ± 29, 390 ± 13, 275 ± 10 to 65 ± 10 for TNBC, ER(+), ER(+)PR(+), ER(+)HER2(+), ER(+)PR(+)HER2(+), PR(+)HER2(+), HER2(+), PR(+) and NATs, respectively. These results show that PMPMEase overexpression in breast cancer may explain the increased enzymatic activity in the tumors. PMPMEase enzymatic activity and/or immunoreactivity may serve as diagnostic procedures for breast cancer. PMPMEase may also serve as valid target for anticancer drug development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1843. doi:1538-7445.AM2012-1843