scholarly journals Correlation between Tumorigenicity and Expression Levels or Splicing Patterns of Transcripts of the Human Papillomavirus Type 16 E6 Gene

1994 ◽  
Vol 85 (4) ◽  
pp. 357-363 ◽  
Author(s):  
Tadao Inoue ◽  
Satoru Kyo ◽  
Tohru Kiyono ◽  
Masahide Ishibashi ◽  
Haruko Ishiwatari ◽  
...  
Gene ◽  
1995 ◽  
Vol 164 (2) ◽  
pp. 373-374 ◽  
Author(s):  
Hiroshi Shirasawa ◽  
Tomoaki Kinoshita ◽  
Yuji Shino ◽  
Kohji Mori ◽  
Kumiko Shimizu ◽  
...  

2001 ◽  
Vol 75 (9) ◽  
pp. 4467-4472 ◽  
Author(s):  
Tim Veldman ◽  
Izumi Horikawa ◽  
J. Carl Barrett ◽  
Richard Schlegel

ABSTRACT The E6 and E7 oncogenes of human papillomavirus type 16 (HPV-16) are sufficient for the immortalization of human genital keratinocytes in vitro. The products of these viral genes associate with p53 and pRb tumor suppressor proteins, respectively, and interfere with their normal growth-regulatory functions. The HPV-16 E6 protein has also been shown to increase the telomerase enzyme activity in primary epithelial cells by an unknown mechanism. We report here that a study using reverse transcription-PCR and RNase protection assays in transduced primary human foreskin keratinocytes (HFKs) shows that the E6 gene (but not the E7 gene) increases telomerase hTERT gene transcription coordinately with E6-induced telomerase activity. In these same cells, the E6 gene induces a 6.5-fold increase in the activity of a 1,165-bp 5′ promoter/regulatory region of the hTERT gene, and this induction is attributable to a minimal 251-bp sequence (−211 to +40). Furthermore, there is a 35-bp region (+5 to +40) within this minimal E6-responsive promoter that is responsible for 60% of E6 activity. Although the minimal hTERT promoter contains Myc-responsive E-box elements and recent studies have suggested a role for Myc protein in hTERT transcriptional control, we found no alterations in the abundance of either c-Myc or c-Mad in E6-transduced HFKs, suggesting that there are other or additional transcription factors critical for regulating hTERT expression.


Virology ◽  
1994 ◽  
Vol 201 (2) ◽  
pp. 388-396 ◽  
Author(s):  
Zhanjiang Liu ◽  
Jyotsna Ghai ◽  
Ronald S. Ostrow ◽  
Ronald C. McGlennen ◽  
Anthony J. Faras

2000 ◽  
Vol 81 (12) ◽  
pp. 2969-2982 ◽  
Author(s):  
Maria Lina Tornesello ◽  
Franco M. Buonaguro ◽  
Luigi Buonaguro ◽  
Immacolata Salatiello ◽  
Elke Beth-Giraldo ◽  
...  

Human papillomavirus type 16 (HPV-16) is the predominant HPV isolate found in malignancies of male and female lower genital tracts. However, only a small percentage of individuals infected with high-risk HPVs develop a genital neoplasia, suggesting that additional events at both the cellular and the virus level are necessary for the progression to cancer, including genetic mutations/rearrangements of viral sequences involved in the oncogenic process. In this study, the genetic stability of the long control region (LCR) (nt 7289–114), which regulates expression levels of oncoproteins E6 and E7, was analysed in HPV-16 isolates from penile carcinoma (PC) biopsies of patients recruited from Uganda, one of the countries with the highest incidence of genital cancers in both men and women. Nucleotide changes within the LCR region typical of the African-1 (Af-1) lineage were observed in all HPV-16 isolates. Two out of five samples showed further rearrangements of the enhancer region. The functional activity of LCR with Af-1 mutations and/or rearrangements was evaluated by cloning each LCR into CAT expression vectors, followed by transfection in several epithelial and non-epithelial cell lines. CAT expression levels driven by a rearranged LCR were significantly higher than those driven by Af-1 or European prototype LCRs. Furthermore, in the NIH3T3 focus formation assay, the transforming activity of E6 and E7 genes, driven by a mutated or rearranged LCR, was 1·4- to 3·0-fold higher, respectively. These results indicate that rearrangements within the LCR of HPV-16 isolated from African PCs are frequently found (2 out of 5, 40%). It is also shown that increased HPV LCR activity is associated with an increased E6/E7-mediated in vitro transforming activity, suggesting that natural variants can play a major role in the pathogenesis of genital carcinomas.


Author(s):  
Katarzyna Sitarz ◽  
Jolanta Kopec ◽  
Barbara Zawilinska ◽  
Malgorzata Klimek ◽  
Slawa Szostek

The E1 and E2 genes of the human papillomavirus encode the so-called early proteins, their sequences are conserved, and regulatory functions are associated with the viral oncoproteins. The purpose of this study is to determine the HPV16 E1 and E2 mutations appearing in the female population of southern Poland, depending on the severity of cervical pathological changes. We also take into account the number of E1 and E2 mutations detected in the E6 gene variant (350G or 350T). This publication is one of the first in the Central and Eastern Europe to deal with this topic. We identified 4 mutations in the E1 gene and 24 mutations in the E2 gene that have not been described so far. In three cases of squamous cell carcinoma a C3409T mutation occurred, which is widely described as oncogenic. This mutation lies in the 3243-3539 area of the E2 hinge region. Statistical analyses show a possible relationship of mutations in this area with oncogenesis. The discovered dependencies may be important in the context of oncogenesis, however, a study with a larger group of patients is needed in order to confirm this view.


2003 ◽  
pp. 275-286
Author(s):  
Norman J. Maitland ◽  
Catherine A. Macintosh ◽  
Christian Schmitz ◽  
Shona H. Lang

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