The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours

Abstract

The closely related small GTP-binding proteins Rac1, Rac2, and Rac3 are part of a larger Rho subfamily of Ras proteins. Because disruption of Ras signaling pathways is relevant to the pathogenesis of a wide variety of cancers, it is important to clearly define the structural and functional characteristics of the participating proteins and their encoding genes. Rho subfamily members are involved in a range of signal transduction pathways relevant to cell growth, differentiation, motility, and stress, and Rac proteins are now recognised as a necessary component of Ras-mediated cellular transformation. We previously mapped RAC3 to chromosome band 17q23→ q25, a region that contains a number of candidate tumour suppressor genes. Because of its oncogenic potential, we have now further refined the location of this gene. Here we confirm that RAC3 maps to chromosome band 17q25.3 and further show that it maps some distance telomeric of a well-characterised minimal breast and ovarian candidate tumour suppressor gene region, BROV. The genomic structure of RAC3, including exon and intron boundaries, is also presented.

Rho-family GTPases: it's not only Rac and Rho (and I like it)

“…It is localized to the membrane to a higher degree than is Rac1 (Mira et al, 2000). Furthermore, it is hyperactive in breast cancers (Mira et al, 2000) and the Rac3 gene is close to a region of chromosome 17 that is often deleted in breast cancers (Morris et al, 2000), which might deregulate its expression.…”

Rac deletion in osteoclasts causes severe osteopetrosis

“…Rac2 is hematopoietic-cell-specific, whereas Rac1 is widely expressed. Rac3 is present in neurons as well as malignant tissue (Haataja et al, 1997;Morris et al, 2000). As osteoclasts express Rac1 and Rac2, we investigated whether these GTPases regulate the bone resorbing capacity of the cell.…”

Rho GTPases and Breast Cancer

“…Deregulation of Rac3, closely related to Rac1, has also been detected in breast cancer (Mira, Benard et al 2000). Rac3 maps to chromosome band 17q25.3, a region known to contain candidate tumor suppressor genes both in breast and ovarian cancers (Morris, Haataja et al 2000). Highly proliferative breast cancer cells, T47D and MCF-7, but not normal breast cell lines, contain constitutively active Rac3 in a Ras-independent manner (Morris, Haataja et al 2000).…”

“…Rac3 maps to chromosome band 17q25.3, a region known to contain candidate tumor suppressor genes both in breast and ovarian cancers (Morris, Haataja et al 2000). Highly proliferative breast cancer cells, T47D and MCF-7, but not normal breast cell lines, contain constitutively active Rac3 in a Ras-independent manner (Morris, Haataja et al 2000). It has also been shown that expression of a dominant negative mutant Rac3 (N17) leads to inhibition of S-phase entry and cellular proliferation in breast tumor cells, which indicate that Rac3 may promote cell growth (Leung, Nagy et al 2003).…”