Michelle Brown

Publications (2)7.06 Total impact

• Article: Truncated forms of BNIP3 act as dominant negatives inhibiting hypoxia-induced cell death.

  Nicolle Bristow, Teralee R Burton, Elizabeth S Henson, Coleen Ong-Justiniano, Michelle Brown, Spencer B Gibson
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  ABSTRACT: BNIP3 (Bcl-2/adenovirus E1B Nineteen Kilodalton Interacting Protein) is a pro-cell death member of the Bcl-2 family of proteins. Its expression is induced by the transcription factor Hypoxia Inducible Factor-1 (HIF-1) under conditions of low oxygen (hypoxia) and is found over expressed in hypoxic regions of many tumors. When over expressed, BNIP3 induces cell death through induction of mitochondrial dysfunction that is dependent on the presence of BNIP3's TM domain. Herein, we have determined that the SkOv3 ovarian cancer cell line expresses a truncated BNIP3 protein, which results in the elimination of the transmembrane domain. Truncation that eliminates all four domains of BNIP3 protein also inhibits hypoxia-induced cell death in SkOv3, HEK293, U251 and MCF-7 cells. Three different mutations in a BNIP3 expression vector that lead to a truncated BNIP3 protein, lacking TM domain only, or lacking CD, BH3, and TM domains resulted in inhibition of hypoxia-induced cell death when transfected into HEK293 cells. We found that truncated BNIP3 failed to associate with the mitochondria and the truncated BNIP3 lacking all four domains can bind to wild type BNIP3. Taken together, truncation of BNIP3 could be a novel mechanism for cancer cells to avoid hypoxia-induced cell death mediated by BNIP3 over expression.
  Biochimica et Biophysica Acta 03/2011; 1812(3):302-11. · 4.66 Impact Factor
• Article: Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads to cell survival mediated though vascular endothelial growth factor expression.

  Sekar Ashok Kumar, Xiaojie Hu, Michelle Brown, Brenda Kuschak, Tiffany A Hernandez, James B Johnston, Spencer B Gibson
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  ABSTRACT: Lysophosphatidic acid (LPA) protects chronic lymphocytic leukemia (CLL) cells from apoptosis. Vascular endothelial growth factor (VEGF) also protects CLL cells against apoptosis. The mechanism for LPA protection against apoptosis in CLL cells is unknown. Herein, we show CLL cells express LPA receptors LPA(1-5) but in normal B cells, LPA(1) was rarely expressed and LPA(3,) LPA(4,) and LPA(6) were undetectable whereas the other LPA receptors were expressed. LPA plasma levels are similar in patients with CLL compared to healthy controls. In contrast, plasma levels of VEGF are elevated in patients with CLL compared to healthy controls and LPA treatment induced VEGF secretion in CLL cells. CLL cells also express VEGF receptors and LPA protection against Flu induced apoptosis is blocked by inhibition of VEGF receptor activation. These results indicate that LPA protects CLL cells from apoptosis through higher expression of LPA receptors and autocrine production of VEGF.
  Leukemia & lymphoma 10/2009; 50(12):2038-48. · 2.40 Impact Factor