Expressions of Rac1, Tiam1 and Cdc42 in retinoblastoma

The Rho GTPases are the molecular regulators of the cell motility processes and are involved in cell cycle progression and gene transcription. We studied the expression of Rho-like GTPases molecules, particularly Rac, Tiam 1 and cdc42, in retinoblastoma and correlated these with clinicopathological parameters of the tumors. Sixty-seven tumors were included which were divided in to two groups; group A: tumors with optic nerve/choroidal/orbital invasion (n = 35) and group B: tumors with no invasion (n = 32). Immunohistochemistry was done on paraffin sections for all the proteins and were confirmed by Western blot on fresh tumor samples. In group A tumors, Rae was positive in 10/35 (28%), cdc42 was positive in 12/35 (34%) and Tiaml was positive in 30/35 (85%) tumors. In group 2 tumors, Rae was positive in 5/32 (15%), cdc42 was positive in 4/32 (12%) and Tiam1 was positive in 30/32 (93%) tumors. Two groups (both invasive and non-invasive tumors) showed decreased expression of Rac1 and cdc42 whereas Tiam1 was significantly expressed in invasive tumors compared to non-invasive tumors (P < 0.0001). We observed a 70 K cleavage product of Tiaml along with an 110 K product by blotting in RB samples. Caspase-3 was also demonstrated in RB samples, which showed Tiaml cleavage products. This is the first study that showed the expression patterns of Rac, cdc42 and Tiaml in retinoblastoma tumors. Thus, further studies are required to prove the involvement of caspase-3 in the cleavage of Tiam I in vitro in RB cells and to trace out alternative pathways involved in tumor progression. (c) 2006 Elsevier Ltd. All rights reserved.