RhoA protein expression in primary breast cancers and matched lymphocytes is associated with progression of the disease

Abstract

RhoA protein is over-expressed in breast cancer and other solid tumors and has been used in tumor biopsies as a quantitative tumor marker for progression, stage and prognosis in molecular detection strategies. Measuring protein markers in plasma or blood cells is preferred to tumor biopsies as it represents a minimally invasive, repeatable measurement that can be followed over time. In this study we evaluated the hypothesis that quantitative RhoA protein expression in circulatory lymphocytes is identically associated with the same tumor clinico-pathological features found in biopsies. RhoA protein levels were analyzed by Western blotting in circulating lymphocytes isolated from 52 consecutive patients with breast cancer and in 34 paired breast tumor biopsies from the same case study, and compared with the following clinico-pathological features of the patients: histological grade, tumor size, steroid receptor status, lymphonode status, proliferative activity and prognosis [Nottingham Prognostic Index (NPI)]. We observed that the level of circulatory, peripheral lymphocyte RhoA expression reflected that found in the matched biopsy of the same patient. Furthermore, similarly to previous reports regarding breast cancer tissue biopsies, the level of RhoA protein expression in both biopsies and in circulatory lymphocytes was positively associated with tumor size, grade, proliferative activity of the tumor biopsy and NPI, while there was no significant association of RhoA protein expression with either estrogen-or progesterone-receptor expression. Our study demonstrated that the association of lymphocyte RhoA protein expression with classical clinico-pathological parameters closely corresponded with that observed for RhoA protein expression in the tumor biopsies. We propose that measurement of RhoA expression in the circulatory lymphocytes of breast cancer patients can be used to predict breast cancer occurrence, progression and prognosis and may prove valuable in the management of cancer patients.

LMO7 Mediates Cell-Specific Activation of the Rho-Myocardin-Related Transcription Factor-Serum Response Factor Pathway and Plays an Important Role in Breast Cancer Cell Migration

“…Together, our study further substantiates an important role for LMO7 in breast cancer metastasis. Therapeutically, although an increased expression of Rho was also demonstrated in metastatic breast cancer (4,5,9,16,27,56,60), Rho may not be a specific target, given its expression in normal cells and its involvement in regulating other important cell functions. LMO7, however, is a cell-specific protein and is not expressed in normal breast tissues (19,47).…”

Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug–Activated Gene 1 Counteracts Intestinal Ulcerative Injuries

“…Enhanced RhoA activity in the cancer cells is mostly due to RhoA overexpression because mutation of RhoA has not been found in human cancers (33,34). Accumulating evidences have shown that upregulation of RhoA mRNA and RhoA protein levels has been well documented in various human cancers (29,30,35). The present study suggests one potent mechanism of epithelial RhoA overexpression via wound-induced NAG-1.…”

“…In contrast, the current study observed elevation of total level of RhoA protein. Upregulation of RhoA expression has been also observed in various types of human cancer cells (29)(30)(31), and one suggested deciphering of the oncogenic induction of RhoA expression is the signaling orchestration by Myc-Skp2-Miz1-p300 transcriptional complex (32). Enhanced RhoA activity in the cancer cells is mostly due to RhoA overexpression because mutation of RhoA has not been found in human cancers (33,34).…”

Forces During Cell Adhesion and Spreading: Implications for Cellular Homeostasis

“…It is also well-known that tumors are stiffer than the surrounding stromal tissue. This stiffening is likely a result of increased interstitial tissue pressure and solid stress due to tumor expansion [120], an increase in the intracellular stiffness of malignant cells [121], excessive RhoA-based cell contractility [122,123], and fibrosis [105]. Furthermore, patients presenting clinically with fibrotic tumors typically have a poor prognosis [124].…”