Research Interests of  Brian Pentecost

Beginning with my Post Doc positions and in the early part of my career at the New York State Department of Health (NYS DoH) I focused on cloning cDNAs/genes and measuring expression. I worked with a mouse model of DES-prenatal exposure and in defining some of the major estrogen-regulated proteins of the mouse uterus As the genome was fleshed out I became more interested in estrogen receptor alpha action/regulation. This involved both the analysis of gene expression and modifications to gene expression in breast cancer cells. I participated in a number of studies with Dr. Arcaro on gene methylation and expression in Tamoxifen-selected cell lines and in tumor samples and recently on analysis of human milk. For the past decade, my principal role within NYS DoH has been the review of germline genetic tests submitted by external clinical labs https://www.wadsworth.org/regulatory/clep/clinical-labs/obtain-permit/test-approval with a recent focus on NGS-based submissions. In many ways I’ve become a generalist and one benefit was the realization that a growing population of reproductive age women was aware of their BRCA status, had an unmet screening need during lactation and that we could reach these women directly.  

Education

Brunel University, Uxbridge, Middlesex, UK  B.Tech (Hons) Institute for Cancer Research, Univ. of London/ UK MRC Toxicology Unit  PhD

Research Training and Employment

1981-1984       Postdoctoral Fellow, Department of Medical Biochemistry, University of Calgary, Canada 1984-1987       Visiting Associate, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 1987-2018       Research Scientist, Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 1988-2016       Assistant Professor, Adjunct Assistant Professor School of Public Health, The State University of New York at Albany. 2018 – pres.    Research Associate, Department of Veterinary & Animal Sciences, University of Massachusetts-Amherst

Publications

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/55228866/?sort=date&direction=descending

Selected Biomedical Research Publications

i). Breastmilk analysis

1. Aslebagh R, Channaveerappa D, Pentecost BT, Arcaro KF, Darie CC. Electrophoresis and Mass Spectrometry-Based Proteomics in Breast Milk for Breast Cancer Biomarker Discovery.  Adv Exp Med Biol. 2019;1140:451-467 PMID: 31347064

ii). Gene methylation and expression in breast cancer: I participated in multiple studies with Dr. Arcaro and the Pathology Dept at Baystate Medical Center on gene expression and methylation in breast tumors with defined characteristics including studies on global gene methylation in primary and second (recurrent) breast tumors and SKP2 expression in triple-negative breast tumors.

1. Williams KE, Jawale RM, Schneider SS, Otis CN, Pentecost BT, Arcaro KF. DNA methylation in breast cancers: Differences based on estrogen receptor status and recurrence. Journal of Cellular Biochemistry. 2018; PMID:30230580
2. Fitzgerald LM, Browne EP, Christie KD, Punska EC, Simmons LO, Williams KE, Pentecost BT, M Jawale R, Otis CN, Arcaro KF. ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors. Cancer Cell International. 2016; 16:8. PMID: 26884724, PMCID: PMC4754800
3. Fagan-Solis KD, Pentecost BT, Gozgit JM, Bentley BA, Marconi SM, Otis CN, Anderton DL, Schneider SS, Arcaro KF. SKP2 overexpression is associated with increased serine 10 phosphorylation of p27 (pSer10p27) in triple-negative breast cancer. Journal of Cellular Physiology. 2014; 229(9):1160-9. PMID: 24443386
4. Gozgit JM, Pentecost BT, Marconi SA, Ricketts-Loriaux RS, Otis CN, Arcaro KF. PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas. British Journal of Cancer. 2007; 97(6):809-17. PMID: 17726467, PMCID: PMC2360386

iii). Cell models for Tamoxifen resistance: I participated in studies to select anti-estrogen (Tamoxifen) resistant variants of MCF. The ER-positive and negative clones were investigated in Dr. Arcaro’s lab; studying gene expression and methylation.  Half of the ER protein in one of the lines lacks the exon 3 encoded DNA binding domain and my lab used stably transfected shRNA expression constructs targeting exon to suppress most of the wild-type ER so we could study ER action in the absence of DNA binding, this circumvented the issues of altered responses in ER-negative cells to which ER constructs are transfected.

1. Williams KE, Anderton DL, Lee MP, Pentecost BT, Arcaro KF. High-density array analysis of DNA methylation in Tamoxifen-resistant breast cancer cell lines. Epigenetics. 2014; 9(2):297-307. PMID: 24225485, PMCID: PMC3962540
2. Gozgit JM, Pentecost BT, Marconi SA, Otis CN, Wu C, Arcaro KF. Use of an aggressive MCF-7 cell line variant, TMX2-28, to study cell invasion in breast cancer. Molecular Cancer Research: MCR. 2006; 4(12):905-13. PMID: 17189381
3. Pentecost BT, Bradley LM, Gierthy JF, Ding Y, Fasco MJ. Gene regulation in an MCF-7 cell line that naturally expresses an estrogen receptor unable to directly bind DNA. Molecular and Cellular Endocrinology. 2005; 238(1-2):9-25 PMID: 15913882
4. Fasco MJ, Amin A, Pentecost BT, Yang Y, Gierthy JF. Phenotypic changes in MCF-7 cells during prolonged exposure to tamoxifen. Molecular and Cellular Endocrinology. 2003; 206(1-2):33-47. PMID: 12943988

iv). Translational control of Estrogen Receptor expression: I conducted studies on the consequences of alternate Estrogen Receptor promoter use. We demonstrated, in studies supported by the CDMRP breast cancer program, that alternate upstream open reading frames have distinct effects on the expression of the common ER open reading frame. We attempted to make antibodies against the peptides as diagnostics (since the capacity to make ER protein relates to promoter use) but were not successful.

1. Pentecost BT, Song R, Luo M, DePasquale JA, Fasco MJ. Upstream regions of the estrogen receptor alpha proximal promoter transcript regulate ER protein expression through a translational mechanism. Molecular and Cellular Endocrinology. 2005; 229(1-2):83-94. PMID: 15607532

v). Steroid regulation of gene expression in the reproductive tract: As a visiting associate with NIEHS and as a research scientist with NY State I had an interest in gene regulation in the reproductive tract. At NIEHS I cloned the cDNA to the major DES-induced protein of the mouse uterus and identified it as Lactoferrin. We then demonstrated anomalous expression of LTF in the mouse seminal vesicles from males prenatally exposed to DES. It remains unknown if this was due to ‘feminization’ of the seminal vesical epithelium or aberrant retention of Mullerian duct elements in the seminal vesicle. At the Wadsworth Center of NY State DoH, with NIDDK R25 support, I cloned sequences to mouse uterine Creatine Kinase B (CKB), the classic mouse uterine estrogen Induced Protein (IP) and demonstrated that estrogen control was via a weak estrogen response element embedded with GC boxes (SP1 binding sites) upstream of the CKB promoter.

1. Pentecost BT, Teng CT. Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions. The Journal of Biological Chemistry. 1987; 262(21):10134-9. PMID: 3611056
2. Newbold RR, Pentecost BT, Yamashita S, Lum K, Miller JV, Nelson P, Blair J, Kong H, Teng C, McLachlan JA. Female gene expression in the seminal vesicle of mice after prenatal exposure to diethylstilbestrol. Endocrinology. 1989; 124(5):2568-76. PMID: 2707167
3. Pentecost BT, Mattheiss L, Dickerman HW, Kumar SA. Estrogen regulation of creatine kinase-B in the rat uterus. Molecular Endocrinology (Baltimore, Md.). 1990; 4(7):1000-10. PMID: 2284002
4. Wu-Peng XS, Pugliese TE, Dickerman HW, Pentecost BT. Delineation of sites mediating estrogen regulation of the rat creatine kinase B gene. Molecular Endocrinology (Baltimore, Md.). 1992; 6(2):231-40. PMID: 1569966