Alternate Splicing of CD44 Messenger RNA in Prostate Cancer Growth
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2009
- Accession Number
- ADA525215
Entities
People
- Alina Handorean
- Eric W. Robbins
- Kenneth A. Iczkowski
- Kui Yang
- Yaqiong Tang
Organizations
- University of Colorado Health