Alternate Splicing of CD44 Messenger RNA in Prostate Cancer Growth
Final rept. 1 Apr 2007-30 Sep 2009
COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
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Aim 1 Loss of CD44 standard and increased splice variant form CD44v7-10 facilitate prostate cancer PC invasion. First Sub-Aim A manuscript was published 2008 on the role of Mitogen-activated protein kinase MAPK pathways and paracrine calcitonin, both of which dysregulate CD44. Second Sub-Aim Metabolic labeling studies of CD44 total and CD44v7-10 protein were pursued over about a 6- month period, but the findings were not publishable. Aim 2 Instead of adeno-associated virus for altering expression of CD44 prior to in vitro and in vivo studies, retroviruses were used. The focus was on PC-3M PC cells. Confirmation of re-expression of CD44s as a 1 Fusion protein with luciferase or 2 Separate protein, or 3 RNAi knockdown of CD44v7-10, was achieved using qRT-PCR, western blot analysis, and IVIS visualization of luminescence after adding luciferin substrate, in a flask or mouse tumor. Cells re-expressing CD44s had decreased growth, decreased Matrigel migration and invasion, decreased anchorage-independent colony formation, and restoration of adhesion to hyaluronan a benign feature. RNAi against CD44v7-10 caused decreased Matrigel invasion and markedly increased Docetaxel chemosensitivity, as the only in vitro changes. All 3 treatments had mild non-significant anti-growth effects on mouse subcutaneous xenografts. A manuscript is under review BMC Cancer. Other 3 manuscripts published on the effect of Silibinin, microRNAs 373 and 520c, and hydantoin compounds, on CD44 expression.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research