Immunohistochemical Staining for Ras-Related Protein 25 (RAB25) Associates with Luminal B Breast Cancer Subtype (original) (raw)
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The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers
Nature Medicine, 2004
High-density array comparative genomic hybridization (CGH) 1 showed amplification of chromosome 1q22 centered on the RAB25 small GTPase 2 , which is implicated in apical vesicle trafficking 3 , in approximately half of ovarian and breast cancers. RAB25 mRNA levels were selectively increased in stage III and IV serous epithelial ovarian cancers compared to other genes within the amplified region, implicating RAB25 as a driving event in the development of the amplicon. Increased DNA copy number or RNA level of RAB25 was associated with markedly decreased disease-free survival or overall survival in ovarian and breast cancers, respectively. Forced expression of RAB25 markedly increased anchorage-dependent and anchorage-independent cell proliferation, prevented apoptosis and anoikis, including that induced by chemotherapy, and increased aggressiveness of cancer cells in vivo. The inhibition of apoptosis was associated with a decrease in expression of the proapoptotic molecules, BAK and BAX, and activation of the antiapoptotic phosphatidylinositol 3 kinase (PI3K) and AKT pathway, providing potential mechanisms for the effects of RAB25 on tumor aggressiveness. Overall, these studies implicate RAB25, and thus the RAB family of small G proteins, in aggressiveness of epithelial cancers.
Involvement of Rab25 Biomarker in Pathogenesis of Ovarian Cancer
Asian Journal of Medicine and Biomedicine, 2021
Ovarian tumor is the third leading common gynecologic tumor and the common leading cause of death in gynecological cancers to the entire global and studies suggested that Rab25 is insinuated in the pathological process of ovarian cancer. Despite the availability of biomarkers for ovarian cancer detection, there are no specific markers that enable the early detection of ovarian cancers which open an avenue to Rab25 to be review. A number of genes and proteins have been reported to be involved in the pathogenesis of ovarian cancers. Of them, Ras-related protein 25 (Rab25) is suggested to be linked to increased risk of ovarian cancer development. Rab25, an intracellular transport protein, belongs to the Rab small GTPase family and regulates various aspects of internalized membrane protein recycling and trafficking occurring inside the cells to the cell membrane. It is known to be involved in cell proliferation, and prevents apoptosis and invasion in ovarian cancer. Rab25 is highly foun...
The secretory small GTPase Rab27B as a marker for breast cancer progression
Oncotarget, 2010
In contemporary oncology practice, an urgent need remains to refine the prognostic assessment of breast cancer. It is still difficult to identify patients with early breast cancer who are likely to benefit from adjuvant chemotherapy. Although invasion of cancer cells is the main prognostic denominator in tumor malignancy, our molecular understanding and diagnosis are often inadequate to cope with this activity. Therefore, deciphering molecular pathways of how tumors invade and metastasize may help in the identification of a useful prognostic marker. We recently discovered that the secretory small GTPase Rab27B, a regulator of vesicle exocytosis, delivers proinvasive signals for increased invasiveness, tumor size, and metastasis of various estrogen receptor (ER)-positive breast cancer cell lines, both in vitro and in vivo. In human breast cancer specimens, the presence of Rab27B protein proved to be associated with a low degree of differentiation and the presence of lymph node metast...
Cancer research, 1986
Monoclonal antibodies RAP-5 and Y13-259, directed against the ras gene product [a protein with a molecular weight of 21,000 (p21)] have been used to evaluate ras p21 expression in malignant and benign mammary tissues as well as in the lesions of intermediate stature such as atypical hyperplasia using immunohistochemical assays. Invasive carcinoma demonstrated enhanced expression of ras p21, with generally decreasing expression in carcinoma in situ, atypical hyperplasia, and nonatypical hyperplasia, respectively. Heterogeneous expression of ras p21 was observed among primary as well as metastatic mammary carcinomas. Carcinomas from postmenopausal patients generally demonstrated higher levels of ras p21 than those from premenopausal patients, but no significant difference in ras p21 expression in carcinomas between estrogen-receptor rich and estrogen-receptor poor patients was found. Normal mammary epithelium in terminal duct lobular units from patients with hyperplasia generally demo...
Oncology Letters
The majority of breast cancer tumors are estrogen receptor-positive (ER +) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER + breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER + tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cutoff for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER +) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER + /PRsubgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER + /PRsubgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER + /PR + tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER + /PRtumor.
Association between the ras p21 oncoprotein in blood samples and breast cancer
Cancer Letters, 2002
To assess the potential of using oncoprotein levels in blood as a marker of breast cancer status, we measured ras p21 in blood samples taken from 34 breast cancer cases and 60 non-cancer controls including 26 women with benign breast disease (BBD) and 34 healthy women. Plasma samples drawn before surgery or at routine office visit were analyzed for ras p21 by Western blot with computer aided image analysis to measure staining intensity in integrated pixel units (IPU). We found detectable levels of ras p21 in 53% of the blood samples of cases, in 27% of the BBD controls and 26% of the healthy controls. Comparing cases to the combined control group (n ¼ 60) and controlling for known breast cancer risk factors, ras p21 was associated with breast cancer status (odds ratio ¼ 5:22, 95% CI ¼ 1:58-17:23). The median levels of ras p21 staining were higher in cases (7.04 IPU, P ¼ 0:03) compared to BBD controls (0.00 IPU) or healthy controls (0.00 IPU). The sensitivity of the assay for detecting breast cancer was 50% which compares favorably with that seen for erbB-2 (,10%), a more extensively studied blood-borne tumor marker. Ras p21 may be useful in the early detection of breast tumors and in post-surgical follow-up of patients, giving patients and physicians new tools for managing breast cancer. q
RAS polymorphisms in cancerous and benign breast tissue
Journal of the Renin-Angiotensin-Aldosterone System, 2010
Recent information has revealed new roles in the angiogenic processes linked to the rennin-angiotensin system. To date few studies have been done on the association between RAS genes and cancer and the majority focus mainly on angiotensin I-converting enzyme (ACE). For breast cancer there are three reports that include the angiotensin II receptor, subtype 1 (AGTR1), only one for angiotensinogen (AGT) and none for renin gene (REN). In the present study we investigate whether REN (BglI), AGT (M235T), ACE (A245T, Indel), and AGTR1 (A1166C) are associated with breast cancer. Polymorphisms were analysed by PCR and RFPLs or sequence specific assay in three groups: breast cancer, benign breast disease (BBD) and general population. REN polymorphism shows that homozygous for A allele have an increased risk for BBD. Differences in M235T genotype frequencies were significant with less heterozygous in breast cancer. With different risk values ACE indel was associated with BBD and breast cancer....
Breast Cancer Research and Treatment, 2008
Purpose To evaluate the pure prognostic impact of the uPA-receptor splice variant uPAR-del4/5 for lymph nodenegative breast cancer patients, and to identify differentially expressed genes associated with high or low uPAR-del4/5 mRNA levels. Patients and methods mRNA transcript levels were measured by real-time PCR in tumor samples from 280 node-negative breast cancer patients who had not received adjuvant systemic therapy. Endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Gene expression analysis was performed with RNA isolated from breast cancer tissue and breast cancer cell lines using Affymetrix U133a GeneChips.