Date of Award
Master of Science (MS)
Cell Biology and Biochemistry
Susan E. Senogles, Ph.D.
Kafait U. Malik, Ph.D., D.Sc. Satoru K. Nishimoto, Ph.D. Rennolds S. Ostrom, Ph.D. Lawrence M. Pfeffer, Ph.D.
Bromocriptine, a D2 dopamine receptor (D2R) agonist, is used clinically as a treatment for pituitary tumors of a lactotroph origin. Many questions remain unanswered about the mechanism of this effect. The antiproliferative effect has not been demonstrated in DMS 53 cell line, a Small Cell Lung Cancer (SCLC). In this thesis, we have shown that treatment with NPA (N‑propylnorapomorphine), a dopamine receptor agonist inhibits ERK phosphorylation and proliferation in DMS 53 cells. NPA treatment causes significant increases in DUSP‑1 (MKP‑1), DUSP‑4 (MKP‑2) and DUSP5 mRNA. NPA treatment also correlates with increases in DUSP5 (hVHR3) protein visualized using Western Blot. These three genes were also induced by treatment with exogenous arachidonic acid (AA). In addition, the NPA mediated increases in these genes was inhibited by 5,8,11,14‑eicosatetraynoic acid (ETYA) an AA analog and inhibitor of downstream activity, suggesting NPA induction of these three genes is AA dependent. Ethanol treatment leads to inhibition of the NPA induction of DUSP4 and DUSP5, suggesting phosphatidic acid (PA) produced from Phospholipase D (PLD) is involved in this induction.
Lattimer, Scott Lemar , "D2R Dopamine Receptor Mediates Changes in Dual Specificity Phosphatase Expression in a Small Cell Lung Cancer Cell Line" (2010). Theses and Dissertations (ETD). Paper 149. http://dx.doi.org/10.21007/etd.cghs.2010.0173.