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Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice
Yuexing Zhang, Yan Lu, Hua Zhou, Myounghee Lee, Zhenqiu Liu, Bret A Hassel, Anne W Hamburger
BMC Cell Biology , 2008, DOI: 10.1186/1471-2121-9-69
Abstract: Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues.These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.Members of the ErbB receptor tyrosine kinase family (ErbB1-4) and their ligands are important regulators of cell growth and differentiation. Studies of ErbB1, ErbB2 and heregulin (the ErbB3/4 ligand) deficient mice indicate that these genes are essential for embryonic development [1]. In turn, the activity of the ErbB receptors is regulated by their interacting partners. An ErbB3 binding protein (Ebp1) was cloned in our laboratory during a yeast two-hybrid screen [2]. Ebp1 is identical to the murine p38-2G4 protein which was isolated as a DNA binding protein[3]. These proteins are members of the Proliferation-associated 2G4 (Pa2g4) gene family, which is highly conserved throughout evolution [4]. More than 30 genes encoding proteins homologous to Ebp1 have been found in organisms ranging from Danio rerio to Pan troglodytes [5].Ebp1 is expressed in mammalian cell lines derived from multiple origins. Ebp1 mRNA is also found in all normal adult human and murine tissues examin
Expression of ErbB3-Binding Protein-1 (EBP1) during Primordial Follicle Formation: Role of Estradiol-17?  [PDF]
Anindit Mukherjee, Shyamal K. Roy
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067068
Abstract: The formation of primordial follicles involves the interaction between the oocytes and surrounding somatic cells, which differentiate into granulosa cells. Estradiol-17? (E) promotes primordial follicle formation in vivo and in vitro; however, the underlying mechanisms are poorly understood. The expression of an ERBB3-binding protein 1 (EBP1) is downregulated in 8-day old hamster ovaries concurrent with the increase in serum estradiol levels and the formation of primordial follicles. The objectives of the present study were to determine the spatio-temporal expression and putative E regulation of EBP1 in ovarian cells during perinatal development with respect to primordial follicle formation. Hamster EBP1 nucleic acid and amino acid sequences were more than 93% and 98% similar, respectively, to those of mouse and human, and contained nucleolar localization signal, RNA-binding domain and several phosphorylation sites. EBP1 protein was present in somatic cells and oocytes from E15, and declined in oocytes by P1 and in somatic cells by P5. Thereafter, EBP1 expression increased through P7 with a transient decline on P8 primarily in interstitial cells. EBP1 mRNA levels mirrored protein expression pattern. E treatment on P1 and P4 upregulated EBP1 expression by P8 whereas E treatment on P4 downregulated it by 72 h suggesting a compensatory upregulation due to E pretreatment. Treatment with an FSH-antiserum, which suppressed primordial follicle formation, prevented the decline in EBP1 levels, and the effect was reversed by E treatment. Therefore, the results provide the first evidence that EBP1 may play an important role in mediating the effect of E in the differentiation of somatic cells into granulosa cells during primordial follicle formation.
Mitochondrial Mutations in Adenoid Cystic Carcinoma of the Salivary Glands  [PDF]
Suhail K. Mithani,Chunbo Shao,Marietta Tan,Ian M. Smith,Joseph A. Califano,Adel K. El-Naggar,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008493
Abstract: The MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas.
Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study  [cached]
Lee Seok Ki,Kwon Min Su,Lee Yoon Se,Choi Seung-Ho
World Journal of Surgical Oncology , 2012, DOI: 10.1186/1477-7819-10-266
Abstract: Background Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated. Methods The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed. Results Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate. Conclusions The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.
Suprabasin Is Hypomethylated and Associated with Metastasis in Salivary Adenoid Cystic Carcinoma  [PDF]
Chunbo Shao,Marietta Tan,Justin A. Bishop,Jia Liu,Weiliang Bai,Daria A. Gaykalova,Takenori Ogawa,Ami R. Vikani,Yuri Agrawal,Ryan J. Li,Myoung Sook Kim,William H. Westra,David Sidransky,Joseph A. Califano,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048582
Abstract: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.
erbB3结合蛋白-ebp1在腺样囊性癌组织中的表达及其临床意义  [PDF]
复旦学报(医学版) , 2010,
Abstract: 目的研究ebp1在涎腺腺样囊性癌中的表达,并探讨其与病理生物学特征及患者术后生存时间的关系,以期为评价ebp1作为涎腺腺样囊性癌早期诊断和患者预后的可能性提供实验依据。方法采用PV6000二步法免疫组化染色检测有完整随访资料的35例涎腺腺样囊性癌及相应癌旁正常组织中ebp1表达的差异。结果正常涎腺组织中ebp1的阳性表达(97.1%)明显高于涎腺腺样囊性癌组织中(74.3%)的表达(P=0.016)。ebp1蛋白表达强度与肿瘤的组织学类型及分期密切相关(P<0.05),但与患者的年龄、性别和侵袭转移类型无明显相关性(P>0.05)。其中,单纯筛状和筛状管状型ACC中ebp1的表达明显高于坏死型;T1-T2期患者中ebp1表达显著高于T3-T4期患者(P<0.05)。此外,ebp1阳性表达组患者的生存期明显高于ebp1阴性表达组,且具统计学差异(P=0.048)。结论ebp1的下调可能促进涎腺腺样囊性癌的发生发展,可考虑作为涎腺腺样囊性癌临床评价肿瘤生物学行为及评估预后的指标。
Adenoid Cystic Carcinoma of Parotid Salivary Gland—A Case Study  [PDF]
Shuaib Kayode Aremu
Case Reports in Clinical Medicine (CRCM) , 2018, DOI: 10.4236/crcm.2018.711052
Abstract: Adenoid Cystic Carcinoma (ACC) is an infrequent slow growing epithelial tumour constituting for around less than 1% of all the oral and maxillo-facial malignancies and almost 10% of all the salivary gland tumors. Parotid gland is the second most common site to be involved in the head and neck region along with submandibular gland, Palate being the most common site involved in the oral cavity. Key feature of these tumors include its asymptomatic presentation, indolent nature, typically showing infiltrative growth and peri-neural invasion. Herein, we report a case of adenoid cystic carcinoma of right parotid gland of a 33-year-old male who presented with complaint of painless slow enlargement of left parotid gland and facial muscle weakness. On Examination firm mass in the region of the left parotid gland as well as left facial paralysis was seen. Biopsy results and further management is discussed here within.
Mucoepidermoid carcinoma of the salivary glands in Brazil: clinicopathological outcomes
Oliveira,Lucinei Roberto; Figueiredo Soave,Danilo; Oliveira-Costa,Jo?o Paulo; Sala Di Matteo,Miguel Angel; Ribeiro-Silva,Alfredo;
Revista Cubana de Estomatolog?-a , 2012,
Abstract: the biological features and clinical behavior of mucoepidermoid carcinomas are widely variable and poorly understood. this study aimed to investigate prognostic factors that may affect survival in patients with a primary diagnosis of head and neck mucoepidermoid carcinomas. the effects of age, gender, anatomic localization, tumor size, clinical stage, histological grade, recurrence, metastasis, compromised surgical margins and treatment on clinicopathological outcomes were investigated. survival curves were generated using the kaplan-meier method and analyses were performed using the log rank test. a total of 16 cases were analyzed over a period of 18 years; males were 68.7 %, with ages ranging from 13 to 83 years. the 75 % of the tumors developed in the major salivary glands, 56.3 % in the parotid gland and they were predominantly classified as stage ii 37.5 % and low-grade lesions 37.5 % at diagnosis. surgical resection was performed in all patients. the follow-up period in this study ranged from 6 to 217 months. the 5 and 10-year overall survival rates were both 85.6 %. disease-free survival rates were 81.8 % (5 years) and 68.2 % (10 years). there were statistically significant effects of tumor size (p= 0.05), metastasis (p= 0.04) and primary anatomic localization (p= 0.04) on disease-free survival rates. through a long follow-up period in present study we could highlight the relevance of primary anatomical site, tumor size and metastasis as useful prognostic factors that may affect survival in patients with a primary diagnosis of head and neck mucoepidermoid carcinomas.
Adenoid basal lesions of the uterine cervix: evolving terminology and clinicopathological concepts
Michael J Russell, Oluwole Fadare
Diagnostic Pathology , 2006, DOI: 10.1186/1746-1596-1-18
Abstract: The historical evolution of the lesions that are currently designated "adenoid basal carcinomas" [1-25] is inextricably linked to adenoid cystic carcinoma [26-84], a diagnostic entity under which it was subsumed for many years prior to and even after its delineation, and a tumor with which it shares some morphologic features and probably, a histogenetic basis. Adenoid cystic carcinoma of the cervix (ACC) was originally described as "cylindroma" by Paalman and Counsellor [84] in 1949. Fifteen years later, Moss and Collins [83] described a distinctive cervical neoplasm that was predominantly comprised of ACC but which also contained foci of small basaloid nests. The authors designated this tumor "adenoid cystic basal carcinoma". However, the 1966 report of Baggish and Woodruff [24], in which the term "adenoid-basal carcinoma" (ABC) was initially used, is widely credited [85-89] with the delineation of this lesion as a separate clinicopathologic entity. The latter authors described 3 examples of a morphologically distinctive cervical tumor that was comprised of small basaloid cells nests that seemed to be "dropping off" the basal layer of the overlying surface epithelium, which did not elicit any significant stromal reaction, and which in all 3 cases, were associated with carcinoma-in-situ of the overlying epithelium. All 3 patients were treated with surgical resections and none had experienced recurrences within the follow-up period. Based in part on the absence of a significant stromal reaction, the authors suggested that the lesions were "only as locally invasive as the basal cell lesion of the skin and demand no more radical therapy than wide local excision" [24]. In a follow-up report [23], all 3 patients were alive and well 5–13 years after their hysterectomies. In the same report, Baggish and Woodruff reported 5 additional cases, introducing the term "adenoid basal hyperplasia" [23] as well as the concept that different malignancies may be associated with ABC. I
Ebp1 expression in benign and malignant prostate
Philippe O Gannon, Isma?l Koumakpayi, Cécile Le Page, Pierre I Karakiewicz, Anne-Marie Mes-Masson, Fred Saad
Cancer Cell International , 2008, DOI: 10.1186/1475-2867-8-18
Abstract: The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.Although not related to disease recurrence, this is the first in vivo study to report that Ebp1 expression correlates with PCa progression.Prostate cancer is a major public health concern in North American and European countries. Through improvements in diagnostic methods and increased awareness, greater than 90% of patients are now being diagnosed with localized or regionally advanced prostate cancer [1]. Nonetheless, between 15% and 35% of patients will develop prostate specific antigen (PSA) relapse within 10 years following surgery [2,3]. As the course of the disease is quite variable, progress needs to be made in the establishment of clinical tests that could help identify patients at risk of recurrence and progression. The molecular characterization of tumor cells through immunohistochemical analysis offers the opportunity to better stratify patien
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