Cellular Expression of INK4a Gene in Cells of Bladder Cancer Associated with Human Papilloma Virus-16

Волгарева, Г. М.; Завалишина, Л Э; Головина, Д. А.; Andreeva, Yu Yu; Ермилова, В. Д.; Trofimova, Olga; Куевда, Д А; Shipulina, O. Yu.; Glazunova, Valeria A.; Cheng, Shuling; Pavlova, L. S.; Чебан, Н. Л.; Матвеев, В. Б.; Франк, Г. А.

doi:10.1007/s10517-010-0917-0

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…Interestingly, 31 and 33% of the carcinomas in that study had also shown positivity for p16 INK4a , and upregulation of p16 INK4a in tumor cells independent of HPV infection has also been described for other tumour entities[35]. Furthermore, a 2010 study showed that even in HPV DNA-positive bladder cancers, p16 INK4a expression did not correlate with the expression of HPV16 E7 oncoprotein[36]. Taking these and our results together, we think that it is not advisable to regard p16 INK4a as a surrogate marker for HPV infection or HPV-associated tumorigenesis in urothelial carcinoma.…”

Section: Discussionmentioning

confidence: 83%

Overexpression of p16INK4a in Urothelial Carcinoma In Situ Is a Marker for MAPK-Mediated Epithelial-Mesenchymal Transition but Is Not Related to Human Papillomavirus Infection

et al. 2013

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BackgroundThe role of human papillomavirus (HPV) in bladder carcinogenesis remains controversial. Overexpression of p16INK4a, a surrogate marker for infection with oncogenic HPV in other tumours, has been described for urothelial carcinoma in situ (UCIS). Our goal was therefore to evaluate whether overexpression of p16INK4a is associated with HPV infection and to identify mechanisms of p16INK4a upregulation in UCIS.Materials and MethodsIn 60 tissue specimens from a total of 45 patients (UCIS and controls), we performed p16INK4a immunohistochemistry followed by detection and subclassification of HPV DNA. In a subset of samples, we tested for gene amplification of p16INK4a applying fluorescence in situ hybridization (FISH). RAS/MAPK signalling and epithelial-mesenchymal transition (EMT) was assessed using immunohistochemistry. Finally, we transfected urothelial carcinoma cells with KRAS and examined the expression of p16INK4a as well as markers of EMT.ResultsWe found overexpression of p16INK4a in 92.6% of UCIS and in all cervical intraepithelial neoplasia (CIN) controls. In contrast, we detected high-risk HPV DNA in 80% of CIN, but none in UCIS. There was no gene amplification of p16INK4a. High levels of phosphorylated kinases and urokinase plasminogen activator (uPA) and loss of membraneous E-cadherin were detected in UCIS. KRAS transfection of urothelial carcinoma cells led to upregulation of p16INK4a and uPA accompanied by loss of E-cadherin that could be inhibited by application of the kinase-inhibitor Sorafenib.ConclusionsOur results show that overexpression of p16INK4a in UCIS is neither associated with HPV infection nor p16INK4a gene amplification but is a consequence of enhanced RAS/MAPK signalling that promotes EMT, possibly due to Sorafenib-sensitive paracrine secretion of the EMT activator uPA. These findings might open a novel therapeutic option for localized but aggressive urothelial cancer.

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Section: Discussionmentioning

confidence: 83%

Overexpression of p16INK4a in Urothelial Carcinoma In Situ Is a Marker for MAPK-Mediated Epithelial-Mesenchymal Transition but Is Not Related to Human Papillomavirus Infection

et al. 2013

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“…2) and respective protein p16 INK4a (Fig. 3) (Volgareva et al, 2010b). The above mentioned phenomenon of the INK4a overexpression indicating to HR-HPV E7 activity in cervical cells served as a rationale.…”

Section: Study Of Ink4a Expression In Dna Hpv16-positive Bladder Cancmentioning

confidence: 89%

Role of HPV in Urothelial Carcinogenesis: Current State of the Problem

Волгарева¹,

Матвеев²,

Головина³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…HPV16 and HPV18 DNA were detected in nearly 50% of urinary bladder dysplasia and carcinoma specimens when examined using in situ hybridization [68]. In another study, HPV16 genetic material was found in 40% of transitional bladder cancer specimens [69]. Despite the results of these studies, the IARC concluded that there is “inadequate evidence” to support a role of HPV in bladder carcinogenesis.…”

Section: Bladder Cancermentioning

confidence: 99%

“…The human polyomaviruses BKV and JCV establish persistent infections in humans and possess oncogenic and transforming potential in experimental animal models and cell cultures [54]. The presence of BKV and JCV were detected in urothelial carcinomas of the renal pelvis RCCs [69]. However, no definitive association between BKV and human cancers has been established to date [70,71].…”

Section: Bladder Cancermentioning

confidence: 99%

The role of infectious agents in urogenital cancers

Alibek

Karatayeva

Bekniyazov

2012

Infect Agents Cancer

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Since the late 1990s, infectious agents have been thought to play a role in the pathogenesis of approximately 15% of cancers. It is now widely accepted that infection of stomach tissue with the bacteria Helicobacter pylori is an important cause of stomach adenocarcinoma. In addition, oncogenic viruses, such as papilloma viruses, herpes viruses, and hepadnaviruses are strongly associated with increased risk of cervical cancer, lymphomas, liver cancer, amongst others. However, in the scientific community the percentage of cancers caused by pathogens is believed to be far higher than 15%. A significant volume of data collected to date show an association between infectious agents and urogenital cancers. These agents include Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium and certain viruses that have been implicated in ovarian cancer. Other pathogens include the hepatitis C and Epstein-Barr viruses, which are potentially involved in kidney cancer. In addition, infections with Schistosoma haematobium, the human papillomavirus, and human polyomaviruses are strongly associated with an increased risk of urinary bladder cancer. This article reviews publications available to date on the role of infectious agents in urogenital cancers. A greater understanding of the role of such agents could aid the identification of novel methods of urogenital cancer treatment.

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Cellular Expression of INK4a Gene in Cells of Bladder Cancer Associated with Human Papilloma Virus-16

Cited by 4 publications

References 10 publications

Overexpression of p16INK4a in Urothelial Carcinoma In Situ Is a Marker for MAPK-Mediated Epithelial-Mesenchymal Transition but Is Not Related to Human Papillomavirus Infection

Overexpression of p16INK4a in Urothelial Carcinoma In Situ Is a Marker for MAPK-Mediated Epithelial-Mesenchymal Transition but Is Not Related to Human Papillomavirus Infection

Role of HPV in Urothelial Carcinogenesis: Current State of the Problem

The role of infectious agents in urogenital cancers

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