A cancer-specific transcriptional
signature in human neoplasia
J. Clin. Invest. Francesco Nicassio, et al. 115:3015 doi:10.1172/JCI24862 [
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Figure 2E1A-induced genes in cell cycle and differentiation. E1A-induced genes were analyzed during cell cycle progression and MSC-differentiation. (
A) Expression levels of representative genes, analyzed by Q–RT-PCR, during cell cycle progression of NIH-3T3. The lowest value in each kinetic was assumed as 1, and other values were normalized to it. Red, cell cycle regulated genes (> 10 fold); orange, poorly cell cycle regulated genes (4–10 fold); blue, not regulated, or marginally regulated, genes (marginally regulated, 2–4 fold: C3orf4, K0648, SF3B1; not regulated, < 2 fold, CML66, FLJ37562, SMU-1, SKIN, and TRPC4AP). The cell cycle phase in which gene expression peaked is also indicated. (
B) Examples of cell cycle regulation in NIH-3T3 (top), HeLa cells (middle), and MCF10A cells (bottom) of representative genes. TRPC4AP, open circles; SKIN, filled circles; XTP1, filled triangles; MGC22679, open triangles. (
C) Representative genes were analyzed during differentiation of primary MSCs. MSCs were grown as proliferating myoblasts (t0) and then induced to differentiate. When committed to differentiation, myocytes undergo first an irreversible cell cycle arrest (characterized by block of DNA synthesis, p21 accumulation, and pRb hypophosphorylation) (t24), followed by phenotypic differentiation (t48) (evidenced by the accumulation of differentiation markers such as myosin heavy chain and muscle creatine kinase), and eventually by cell fusion (t72). Transcript levels were measured by Q–RT-PCR every 24 hours during differentiation and normalized to undifferentiated myoblasts (t0). Red indicates the time window in which the highest degree of regulation was detected.