Analysis of RIN1 gene expression in colorectal cancer

Abstract

The RIN1 gene, located on chromosome 11q13.2, is a molecule consisting of a coding region of 2352 bp, has a domain on the 3' side that binds to H-Ras protein, and is presumed to be an important molecule in an intracellular signaling pathway. Since the RIN1 molecule belonging to the effector molecules of H-Ras has not been reported in colorectal or other digestive tract cancers to date, we investigated how the RIN1 gene was involved in colorectal cancer. Fifty-two (51.5%) of 101 colorectal cancer specimens strongly expressed the RIN1 gene compared to the adjacent normal colorectal tissue. The 5-year survival rate of patients positive for the expression of the RIN1 gene was significantly poorer at 55% than that (83%) of patients negative for the expression of the RIN1 gene. Also, we confirmed that RIN1 protein was localized chiefly in the cytoplasm of colorectal cancer cell lines, and bound to 14-3-3 protein, but not to Ras protein.These results indicate that the RIN1 gene serves as an important signal transduction system for evaluating the malignancy of colorectal cancer. Materials and methodsCell culture. The human colorectal cancer cell lines, SW480, LoVo, DLD1, and HT29, were cultured at 37˚C in 5% CO 2 in RPMI-1640 containing 10% heat-inactivated fetal calf serum.Patients and tissue samples. The tissue specimens examined were taken from 101 colorectal cancer patients who underwent resection. Immediately after resection, necrotic and ulcerated parts of the tumors were removed and normal colorectal mucosae were dissociated from the muscle and connective tissues. All tissue specimens were then frozen in liquid nitrogen and stored at -80˚C.All patients had been treated at the First Department of Surgery, University of Fukui, between 1990 and 2000. One hundred and twenty patients consisted of 10 with stage I; 45 with stage II; 25 with stage III; and 21 with stage IV cancers

Endocytosis and Cancer

“…A similar prognostic correlation was reported in non-small-cell lung cancer and in gastric tumors (Wang et al 2012). In colorectal tumors, Rin1 expression correlated not only with poor prognosis but also with venous invasion (Senda et al 2007). Congruent with growth-factor-driven invasiveness and metastasis, studies performed on lung cancer cell lines suggested that Rin1 regulates cell proliferation through EGFR (Tomshine et al 2009).…”

Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana

“…From this present study, RIN1 was localized at the cytoplasm in the head and neck tumor tissues (Figs 2 and 3). This is consistent with a study by Senda et al (2007). From their study, RIN1 was found in the cytoplasm of colorectal cancer.…”

“…This is similar to a study by Milstein et al (2007), who observed that the level of RIN1 was silenced in breast tumor tissues. In contrast, RIN1 expression levels were reported to be elevated in various tumors, including gastric adenocarcinoma [ 19 ], colorectal cancer [ 17 ], non-small cell lung cancer [ 12 ], and bladder urothelial carcinoma [ 20 ]. RIN1 transcript levels from head and neck tumors and normal head and neck tissues were also determined with real-time polymerase chain reaction (RT-PCR) ( Fig 1 ).…”

“…This presents the need for research into possible genes such as RIN1 which encodes a protein regulating epithelial cell properties, and whose expression is found altered in cancerous breast and colorectal epithelial cells [ 9 , 17 ]. The purpose of this study is thus to provide useful information about the level of RIN1 expression in head and neck tumors, which may provide baseline data to facilitate the identification of new molecular targeted therapeutics.…”

Cell Proliferation and Epidermal Growth Factor Signaling in Non-small Cell Lung Adenocarcinoma Cell Lines Are Dependent on Rin1

“…Furthermore, Ras occupation of the Rin1 Ras association domain positively impacts the Rab5 GEF activity of Rin1, which promotes EGFR internalization and attenuation in fibroblasts (23). However, Rin1 expression is up-regulated in several types of cancers, including squamous cell carcinoma (24), colorectal cancer (25), and cervical cancer (26), through duplications or rearrangements of the RIN1 locus. These studies suggest that Rin1 may also play a role in enhancing cell proliferation.…”