Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis

Abstract

Ras homolog (Rho) family small GTPases are critical regulators of actin cytoskeletal organization, cell motility, proliferation, and survival. Surprisingly, the large majority of the studies underlying our knowledge of Rho protein function have been carried out in cultured cells, and it is only recently that researchers have begun to assess Rho GTPase regulation and function in vivo. The purpose of this review is to evaluate our current knowledge of Rho GTPase function in mouse mammary gland development, tumorigenesis and metastasis. Although our knowledge is still incomplete, these studies are already uncovering important themes as to the physiological roles of Rho GTPase signaling in normal mammary gland development and function. Essential contributions of Rho proteins to breast cancer initiation, tumor progression, and metastatic dissemination have also been identified.

Figure 1.

Regulation of Rho GTPase signaling by GEFs, GAPs, and GDIs.

Figure 2.

Mouse mammary gland development. The nipple and rudimentary ducts form during embryogenesis. During puberty, the ductal tree expands to fill the mammary fat pad. Milk producing alveoli are formed during pregnancy and disassembled during involution. Rho GTPases, their regulators and effectors that have been shown to control each stage of mammary gland development are shown.

Figure 3.

Rho GTPases in mouse models of breast cancer. Breast cancer cells leave a tumor residing in the ductal network, enter the circulation, and metastasize to the lungs. Rho proteins and their regulators that have been implicated in these processes are shown.