Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells

Background: In breast cancer, the HER2/neu oncoprotein, which belongs to the epidermal growth factor receptor family, may trigger activation of the phosphoinositide-3 kinase (PI3K)/Akt pathway, which controls cell proliferation, survival, migration, and invasion. In this study, we examined the question of whether or not adenine nucleotide translocase 2 (ANT2) short hairpin RNA (shRNA)-mediated down-regulation of HER2/neu and inhibitory effects on the PI3K/Akt signaling pathway suppressed migration and invasiveness of breast cancer cells. Methods: We utilized an ANT2 vector-based RNA interference approach to inhibition of ANT2 expression, and the HER2/neu-overexpressing human breast cancer cell line, SK-BR3, was used throughout the study. Results: In this study, ANT2 shRNA decreased HER2/neu protein levels by promoting degradation of HER2/neu protein through dissociation from heat shock protein 90 (HSP90). As a result, ANT2 shRNA induced inhibitory effects on the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling by ANT2 shRNA caused down-regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells. Conclusions: These results indicate that knock-down of ANT2 by shRNA down-regulates HER2/neu through suppression of HSP90`s function and inhibits the PI3K/Akt signaling pathway, resulting ultimately in suppressed migration and invasion of breast cancer cells.Wang S, 2009, MOL CANCER, V8, DOI 10.1186/1476-4598-8-81MAHMUT Y, 2009, CANC METASTASIS REV, V28, P15Jang JY, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr1857Ono M, 2006, CLIN CANCER RES, V12, P7242, DOI 10.1158/1078-0432.CCR-06-0646Stirling PC, 2006, NAT STRUCT MOL BIOL, V13, P865, DOI 10.1038/nsmb1153Le Bras M, 2006, CANCER RES, V66, P9143, DOI 10.1158/0008-5472.CAN-05-4407Scaltriti M, 2006, CLIN CANCER RES, V12, P5268, DOI 10.1158/1078-0432.CCR-06-1554ERIC I, 2006, AM J PHYSIOL-CELL PH, V291, P579Romond EH, 2005, NEW ENGL J MED, V353, P1673Piccart-Gebhart MJ, 2005, NEW ENGL J MED, V353, P1659Chevrollier A, 2005, J BIOENERG BIOMEMBR, V37, P307, DOI 10.1007/s10863-005-8642-5Meares GP, 2004, FEBS LETT, V574, P181, DOI 10.1016/j.febslet.2004.08.026Sreedhar AS, 2004, FEBS LETT, V562, P11Citri A, 2004, CELL CYCLE, V3, P51Luciakova K, 2003, J BIOL CHEM, V278, P30624, DOI 10.1074/jbc.M303530200Rao JS, 2003, NAT REV CANCER, V3, P489, DOI 10.1038/nrc1121Val JFF, 2002, CANCER GENET CYTOGEN, V138, P69GARCIARUIZ C, 2002, J BIOL CHEM, V277, P16396Slamon DJ, 2001, NEW ENGL J MED, V344, P783Prenzel N, 2001, ENDOCR-RELAT CANCER, V8, P11Braun S, 2001, CANCER RES, V61, P1890Xu WP, 2001, J BIOL CHEM, V276, P3702Sternlicht MD, 2001, ANNU REV CELL DEV BI, V17, P463Greenlee RT, 2001, CA-CANCER J CLIN, V51, P15Fang JM, 2000, P NATL ACAD SCI USA, V97, P3884Clynes RA, 2000, NAT MED, V6, P443Zhou BP, 2000, J BIOL CHEM, V275, P8027Menard S, 2000, J CELL PHYSIOL, V182, P150Cobleigh MA, 1999, J CLIN ONCOL, V17, P2639Pegram MD, 1998, J CLIN ONCOL, V16, P2659Fiore C, 1998, BIOCHIMIE, V80, P137WOLFGANG HS, 1998, J CELL BIOL, V143, P901Werb Z, 1997, CELL, V91, P439Baselga J, 1996, J CLIN ONCOL, V14, P737CORNELIUS LA, 1995, J INVEST DERMATOL, V105, P170HANEMAAIJER R, 1993, BIOCHEM J, V296, P803UNEMORI EN, 1990, J BIOL CHEM, V265, P445MIGNATTI P, 1989, J CELL BIOL, V108, P671SLAMON DJ, 1987, SCIENCE, V235, P177

Corneal Perforation with Preseptal Cellulitis in a Patient with Acute Lymphocytic Leukemia

We report a case of corneal perforation with preseptal cellulitis in a patient with acute lymphocytic leukemia (ALL). A 17-yr-old female patient who was undergoing combination chemotherapy for ALL was referred due to upper lid swelling and pain in the right eye for 2 days. Visual acuity in the right eye was 20/20. Initial examination showed no abnormal findings, other than swelling of the right upper eyelid. Computed tomography showed a finding of preseptal cellulitis. Microbiologic study of bloody and purulent discharge revealed Serratia marcescens. Corneal melting and perforation with iris prolapse were detected in the right eye on the 16th day. Emergent tectonic keratoplasty was performed. Seven months after surgery, visual acuity in the right eye was 20/300, and the corneal graft was stable

The prevalence and risk factors for pterygium in South Korea: the Korea National Health and Nutrition Examination Survey

OBJECTIVES: To determine the prevalence and risk factors for pterygium in the adult Korean population of South Korea. METHODS: Data were analyzed from 9,193 participants who were 40 years of age or older from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2009 to 2010. Standardized slit-lamp examinations were performed by study ophthalmologists to examine the anterior segment for evidence of pterygium. Pterygium was graded clinically as T1 (atrophic), T2 (intermediate), or T3 (opaque). Every participant underwent ocular and systemic examinations, as well as interviewer-administered questionnaires. Any evidence of pterygium and observed association between the risk factors were recorded. RESULTS: The mean age of the subjects was 55.7 (± 0.2) years. Of the 9,193 eligible subjects, 935 had pterygium in at least one eye. In a multivariate logistic regression analysis adjusted for age and sex, pterygium was significantly associated with rural vs. urban residence (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.4 to 2.0), lower level of education (OR, 4.5; 95% CI, 3.1 to 6.6), low income (OR, 1.3; 95% CI, 1.0 to 1.8), smoking (OR, 0.7; 95% CI, 0.5 to 1.0), and more hours of sun exposure (OR, 1.5; 95% CI, 1.2 to 1.8). After adjusting for all variables, the prevalence of pterygium was significantly associated with age, sex, residence, education level, and smoking. CONCLUSIONS: This is a nationwide epidemiologic study in South Korea to assess the prevalence of and risk factors for pterygium. The overall prevalence of pterygium was 8.8% among Koreans aged 40 years or older. Older age, male gender, rural residence, lower level of education, and non-smoking were associated with the development of pterygium

A Case of Necrotizing Keratoscleritis in Primary Sjogren's Syndrome

We report on a case of necrotizing keratoscleritis in primary Sjogren's syndrome. A 66-year-old female patient who was complaining of ocular pain, tearing and decreased vision in her right eye for the previous two days was admitted to our hospital. Visual acuity in the right eye was hand movement, and initial examination showed a 3.0 × 1.8 mm uveal mass bulging through a corneoscleral melting site in the nasal region of the right eye. Positive anti-nuclear antibody was identified at a titer of 1:320 with a speckled pattern, and both Sjogren's syndrome A and Sjogren's syndrome B antibody tests were positive, with titers >200 U/mL. A technetium 99m pertechnetate salivary scan revealed chronic sialoadenitis in the submandibular glands. We diagnosed the lesion as necrotizing keratoscleritis due to primary Sjogren's syndrome. A corneoscleral patch graft was performed, followed by immunosuppression including oral cyclosporin and topical prednisolone. During a follow-up period of 12 months, the corneoscleral graft was well maintained with no recurrence