van Golen K L, Wu Z F, Qiao X T, Bao L W, Merajver S D
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0948, USA.
Cancer Res. 2000 Oct 15;60(20):5832-8.
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. In a previous study, we identified specific genetic alterations of IBC that could account for a highly invasive phenotype. RhoC GTPase was overexpressed in 90% of IBC archival tumor samples, but not in stage-matched, non-IBC tumors. To study the role of RhoC GTPase in contributing to an IBC-like phenotype, we generated stable transfectants of human mammary epithelial cells overexpressing the RhoC gene. The HME-RhoC transfectants formed large colonies under anchorage-independent growth conditions, were more motile, and were invasive. In conjunction with an increase in motility, overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Furthermore, orthotopic injection into immunocompromised mice led to tumor formation. Taken together, these data indicate that RhoC GTPase is a transforming oncogene in human mammary epithelial cells and can lead to a highly invasive phenotype, akin to that seen in IBC.
炎性乳腺癌（IBC）是最具侵袭性的乳腺癌形式，在表型上与其他形式的局部晚期乳腺癌不同。在先前的一项研究中，我们确定了IBC的特定基因改变，这些改变可能解释其高度侵袭性表型。RhoC GTP酶在90%的IBC存档肿瘤样本中过度表达，但在分期匹配的非IBC肿瘤中未过度表达。为了研究RhoC GTP酶在促成IBC样表型中的作用，我们构建了过表达RhoC基因的人乳腺上皮细胞稳定转染体。HME-RhoC转染体在非贴壁生长条件下形成大菌落，运动性更强且具有侵袭性。随着运动性增加，RhoC的过度表达导致肌动蛋白应力纤维增加和粘着斑接触形成增加。此外，原位注射到免疫受损小鼠体内会导致肿瘤形成。综上所述，这些数据表明RhoC GTP酶是人类乳腺上皮细胞中的一种转化癌基因，可导致高度侵袭性表型，类似于IBC中所见的表型。
