Butler, Andrew P.

Butler, Andrew P. Ph.D.

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Research Interests

Transcriptional regulation, signal transduction, cell cycle, skin cancer

Current Research

My laboratory is interested in regulation of genes involved in cell proliferation and cell cycle control, whose deregulation contributes to the development of cancer.

In one project, we are collaborating with Dr. Rodney Nairn to investigate regulation of cell-cycle related genes in Xiphophorus fish. Interspecies hybrids of Xiphophorus represent a genetic model for melanoma susceptibility. In this model, a p16 homologue (CDKN2A/B) has been identified as a candidate tumor suppressor gene. Because p16 has been implicated in the development of human melanoma, this is an excellent model in which to investigate the role of p16 in cancer. We are characterizing the transcriptional regulation of CDKN2A/B, as well as its interactions with other proteins involved in G1 checkpoint control. Our analysis of the CDKN2A/B promoter demonstrates that CDKN2A/B transcription is aberrantly regulated in melanoma cells, and we have identified a region of the promoter that confers high levels of expression in melanoma. We have also demonstrated that deregulation of CDKN2A/B expression correlates with expression of the Xmrk oncogene. Current studies are aimed at investigating the signaling pathways and transcription factors involved in CDKN2A/B expression in melanoma.

In a related study, we cloned a Xiphophorus forkhead transcription factor, FoxO5, and have begun to characterize its role in regulation of cell proliferation and apoptosis. FoxO transcription factors are regulated by signal transduction pathways activating the Akt protein kinase, and we are using siRNA approaches to investigate the effects of aberrant signaling in melanoma on the ability of FoxO5 to regulate cell proliferation. We are also characterizing the effects on cell growth of FoxO5 mutants which are either constitutively active or dominant negative transcription factors. In a collaboration with Dr. Dean Tang’s laboratory, we have extended our studies of the FoxO transcription factors to human cancer cells.

A second group of transcription factors that we study is the Sp family. We first demonstrated that Sp1 is essential for transcription of mammalian ornithine decarboxylase (ODC), a key gene in tumor promotion and cell proliferation, and that the related transcription factor Sp3 represses ODC and other critical cancer genes. Furthermore, we showed that transcriptional activity of Sp1 is regulated by growth factors and is also increased in epidermal tumors. These relationships are highly conserved, as we have recently found that Sp3 appears to also negatively regulate CDKN2A/B in the Xiphophorus model.

Selected Publications

  1. Butler AP, Trono D, Beard R, Fraijo R, Nairn RS. Melanoma susceptibility and cell cycle genes in Xiphophorus hybrids, Mol Carcinog, 46 (8), 685-91, 2007
  2. Butler AP, Trono D, Coletta LD, Beard R, Fraijo R, Kazianis S, Nairn RS. Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma, Comp Biochem Physiol C Toxicol Pharmacol, 145 (1), 145-55, 2007
  3. Liu J, Chandra D, Rudd MD, Butler AP, Pallotta V, Brown D, Coffer PJ, Tang DG. Induction of prosurvival molecules by apoptotic stimuli: involvement of FOX03a and ROS, Oncogene, 24 (12), 2020-31, 2005
  4. Nairn RS, Kazianis S, Della Coletta L, Trono D, Butler AP, Walter RB, Morizot DC. Genetic analysis of susceptibility to spontaneous and UV-induced carcinogenesis in Xiphophorus hybrid fish, Mar Biotechnol (NY), 3 (Supplement 1), S24-36, 2001
  5. Rudd MD, Johnston DA, Kazianis S, Butler AP. Cloning and analysis of a FoxO transcription factor from Xiphophorus, Gene, 302 (1-2), 31-41, 2003
  6. Kumar AP, Butler AP. Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1, Nucleic Acids Res, 25 (10), 2012-9, 1997
  7. Kumar AP, Mar PK, Zhao B, Montgomery RL, Kang DC, Butler AP. Regulation of rat ornithine decarboxylase promoter activity by binding of transcription factor Sp1, J Biol Chem, 270 (9), 4341-8, 1995

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9438