Shc family expression in neuroblastoma: high expression of shcC is associated with a poor prognosis in advanced neuroblastoma.
نویسندگان
چکیده
The biological features and prognosis of neuroblastoma, a neural crest-derived pediatric tumor, are closely associated with expression of the Trk receptor. Because the Shc family proteins (ShcA, ShcB, and ShcC) are adaptors for various receptors, including Trk receptors, and are regulators of neuronal cell development, we speculated that they may play a role in neuroblastoma. Therefore, in this study, we used semiquantitative reverse transcription-PCR to examine the expression of these three genes in 15 neuroblastoma cell lines, an all-trans-retinoic acid-treated neuroblastoma cell line, and 52 tumor samples. In neuroblastoma cell lines and tumor samples, shcA was ubiquitously and highly expressed. Little expression of shcA was observed. Also, shcB was hardly expressed in neuroblastoma cell lines, but its expression in RT-BM-1 cells was enhanced after all-trans-retinoic acid-induced differentiation, and it was highly expressed in low-stage tumors (P = 0.0095). This suggests that ShcB participates in cellular differentiation and may correlate with a favorable prognosis in neuroblastoma. Finally, the expression of shcC was observed in most of the neuroblastoma cell lines and in some stage 4 patients. Patients with a high expression of shcC had a very poor prognosis (P < 0.0001) and amplification of MYCN, and all died within 31 months after diagnosis. Therefore, ShcC seems to be associated with an aggressive tumor phenotype, perhaps by enhancing TrkB signals. Our results suggest that the expressions of shcB and shcC are important biological factors in neuroblastoma and are useful prognostic indicators.
منابع مشابه
Comparison of the Initial Treatment Results of N-myc Positive and N-myc Negative Neuroblastoma Patients
Background: Neuroblastoma is the most common extra cranial malignant solid tumor of childhood. Various molecular and cytogenetic factors have been implicated in the pathogenesis of neuroblastoma, some of which have proven useful in predicting clinical behavior. Over expression of the oncogen N-myc, is an important indicator of prognosis. Materials and Methods: Our study was performed from 20...
متن کاملHerpes Simplex Virus Type 1 Latency-Associated Transcript Reduces Human Neuroblastoma Cell Proliferation
Background and Aims: The latency-associated transcript (LAT) transcribed by latent Herpes Simplex Virus type-1 in neuron cells are able to influence their host cell pathways. While the most of previous studies were focused on anti-apoptotic effects of LAT, our investigation is making an effort to explore LAT potency on cell cycle pathway in neuroblastoma cell lines. Methods: The evaluation of L...
متن کاملNeuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B
BACKGROUND UBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology. METHODS We evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor...
متن کاملExpression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro.
Members of the multidrug resistance-associated protein (MRP) family of transporters are believed to contribute to cytotoxic drug resistance and chemotherapy failure. We observed frequent MRP4 overexpression in aggressive primary neuroblastoma, a disease for which we have previously shown MRP1 to be a prognostic indicator. High MRP4 expression correlated with MYCN oncogene amplification and was ...
متن کاملAn Unfavorable Metastatic Site at Initial Diagnosis in a 2-year-old Boy with Neuroblastoma
Neuroblastoma (NB) is considered one of the malignant tumors of the nervous system which originates from primordial neural crest cell and is known as the most common extra-cranial solid tumor in childhood. This tumor which is often intra-abdominal, metastases in various sites including the skull, long bones, liver, bone marrow and lymph nodes, but lung metastasis at initial diagnosis is rare (0...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Clinical cancer research : an official journal of the American Association for Cancer Research
دوره 11 9 شماره
صفحات -
تاریخ انتشار 2005