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Steven Safe

Safe, Steven
Steven Safe
Distinguished Professor of Veterinary Physiology and Pharmacology and of Biochemistry and Biophysics Syd Kyle Chair in Veterinary Medicine
VB / Room 410
Undergraduate Education
B.S. Queens University (1962)
Graduate Education
D.Phil. Oxford University (1966)
Postdoc. Oxford and Harvard Universities (1966-68)
Joined Texas A&M in 1981

Molecular Biology of Endocrine Disruption Chemicals

The aryl hydrocarbon receptor (AhR) is a nuclear helix-loop-helix transcription factor which forms a ligand-induced nuclear heterodimer with the AhR nuclear translocator (Arnt) protein. Research in this laboratory is focused on the molecular mechanism of crosstalk between the AhR and estrogen receptor (ER) signaling pathways in which the AhR inhibits estrogen-induced gene expression. The antiestrogenic activities of some AhR agonists are also being developed as drugs for clinical treatment of breast and endometrial cancers in women. Research on estrogen-dependent gene expression in various cancer cell lines is focused on analysis of several gene promoters to determine the mechanisms of ERa and ERb action. This includes several genes that are activated through interactions of the ER with Sp1 protein and other DNA-bound transcription factors.

Recent Publications

  1. Draz, H, Goldberg, AA, Titorenko, VI, Tomlinson Guns, ES, Safe, SH, Sanderson, JT et al.. Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-activated protein kinase (AMPK). Cell. Signal. 2017;40 :172-182.
    doi: 10.1016/j.cellsig.2017.09.006. PubMed PMID:28923415. .

  2. Godugu, C, Doddapaneni, R, Safe, SH, Singh, M. Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer. Eur J Pharm Biopharm. 2016;108 :168-179.
    doi: 10.1016/j.ejpb.2016.08.006. PubMed PMID:27586082. PubMed Central PMC5725228.

  3. Goldberg, AA, Draz, H, Montes-Grajales, D, Olivero-Verbél, J, Safe, SH, Sanderson, JT et al.. 3,3'-Diindolylmethane (DIM) and its ring-substituted halogenated analogs (ring-DIMs) induce differential mechanisms of survival and death in androgen-dependent and -independent prostate cancer cells. Genes Cancer. 2015;6 (5-6):265-280.
    . PubMed PMID:26124925. PubMed Central PMC4482247.

  4. Phillips, TD, Richardson, M, Cheng, YS, He, L, McDonald, TJ, Cizmas, LH et al.. Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures. Arch. Toxicol. 2015;89 (6):967-77.
    doi: 10.1007/s00204-014-1285-8. PubMed PMID:24888377. PubMed Central PMC4254891.

  5. Ying, W, Cheruku, PS, Bazer, FW, Safe, SH, Zhou, B. Investigation of macrophage polarization using bone marrow derived macrophages. J Vis Exp. 2013; (76):.
    doi: 10.3791/50323. PubMed PMID:23851980. PubMed Central PMC3728835.

  6. Safe, SH, Prather, PL, Brents, LK, Chadalapaka, G, Jutooru, I. Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs. Anticancer Agents Med Chem. 2012;12 (10):1211-20.
    . PubMed PMID:22583404. PubMed Central PMC3532564.

  7. Sreevalsan, S, Joseph, S, Jutooru, I, Chadalapaka, G, Safe, SH. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Anticancer Res. 2011;31 (11):3799-807.
    . PubMed PMID:22110202. PubMed Central PMC3280884.

  8. Bredfeldt, TG, Greathouse, KL, Safe, SH, Hung, MC, Bedford, MT, Walker, CL et al.. Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. Mol. Endocrinol. 2010;24 (5):993-1006.
    doi: 10.1210/me.2009-0438. PubMed PMID:20351197. PubMed Central PMC2870935.

  9. Reddivari, L, Vanamala, J, Chintharlapalli, S, Safe, SH, Miller, JC Jr. Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis. 2007;28 (10):2227-35.
    doi: 10.1093/carcin/bgm117. PubMed PMID:17522067. .

  10. Konopleva, M, Zhang, W, Shi, YX, McQueen, T, Tsao, T, Abdelrahim, M et al.. Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells. Mol. Cancer Ther. 2006;5 (2):317-28.
    doi: 10.1158/1535-7163.MCT-05-0350. PubMed PMID:16505105. .

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