Evidence for a pro-apoptotic function of RACK1 in human breast cancer

Abstract

We have read with great interest the recent article by Mamidipudi and Cartwright (2009), in which the authors showed that RACK1 induced apoptosis of human colon cells by inhibiting the expression of antiapoptotic pathways and Src activity, thus leading to death of colon cancer cells.We have recently conducted an analysis of RACK1 messenger RNA (mRNA) expression in 127 human breast cancer and 33 non-cancerous breast tissue specimens. The study was carried out using reverse transcriptase-polymerase chain reaction following RNA extraction from frozen samples. The mRNA copy numbers for RACK1 were normalized against the epithelial marker CK19 as previously described (Al Sarakbi et al., 2009) in order to adjust for epithelial cellularity in the specimens examined. We observed that RACK1 expression levels were higher in the normal breast tissue compared with the cancer specimens (mean levels were 136 vs 32 in paired samples, P ¼ 0.44). Furthermore, RACK1 mRNA levels were significantly lower in TNM3 tumours compared with TNM1 tumours (0.08 vs 33, P ¼ 0.04). After a median followup of 10 years, high levels of RACK1 mRNA expression were associated with a good clinical outcome. The mean level of expression in patients who remained disease-free was 36 compared with 2.4 in those who had systemic relapse (P ¼ 0.042) or those who had local recurrence (mean ¼ 3.86, P ¼ 0.05).Our results are consistent with the authors' observation that RACK1 has a novel pre-apoptotic function in human malignancy. However, our results contradict a recent study that looked at the protein expression of RACK1 in human breast cancer and showed that high levels were predictive of a poor clinical outcome (Cao et al., 2009). Further research is required in order to establish the role of RACK1 as an independent prognostic indicator in human cancer.

The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

“…31 Interestingly, it has been recently described as a pro-apoptotic gene in human breast and colon cancer. 34 Finally, the chromosomal regions where these snoRNAs are located (see Table 1) have been previously reported by us to be transcriptionally active or specifically downregulated in HD patients. 18 Based on these findings, it could be suggested that snoRNAs expression in HD samples may have a role in the overall upregulation of the translational machinery.…”

RACK1, A multifaceted scaffolding protein: Structure and function

“…Specifically, RACK1 expression is being assessed as a prognostic indicator in breast cancer [203,204], where increased RACK1 expression is strongly related to advanced clinical stage [205]. In pulmonary adenocarcinomas, increased RACK1 expression is associated with pathological stage and tumor size and is also a potential diagnostic marker [206].…”

“…In contrast, some reports suggest that RACK1 expression is reduced in breast cancer [207]. In addition, RACK1 may protect cells from apoptosis in breast cancer [204,208]. RACK1 is upregulated in hepatocellular carcinoma where it increases the translocation of A Disintegrin And Metalloprotease 12 (ADAM12) to the plasma membrane in response to PKC activation [209] and it is upregulated in metastatic melanoma, where it amplifies PKCα and PKCβ activity [210].…”

Up-Regulation of RACK1 by TGF-β1 Promotes Hepatic Fibrosis in Mice

“…RACK1 possesses the capacity for interaction with diverse proteins and plays important roles in a variety of physiological functions. The altered RACK1 expression has been identified in several kinds of human diseases, including brain developmental disorders, heart failure, muscle atrophy, breast cancer and pulmonary adenocarcinomas [16], [17], [18], and our previous research also indicates that RACK1 is frequently up-regulated in hepatocellular carcinoma and promotes its chemo-resistance and growth [19]. However, the role of RACK1 in liver fibrosis is little defined.…”