Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells

Bedell, Mary A.; Jones, Katherine H.; Grossman, Steven R.; Laimins, Laimonis A.

doi:10.1128/jvi.63.3.1247-1255.1989

Cited by 158 publications

(55 citation statements)

References 45 publications

(74 reference statements)

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“…'For subjects with multiple-type infection, HPV ty e was assigned hierarchically to the highest risk group applicable based on the excluded-3~w-grade cervical neoplasia, including CIN IsHigh-grade cervical neoplasia, including CIN 2, CIN 3 and invasive can~er-~Adjusted for age at screening-%uAuded 3 low-grade cases and 6 controls with a low level of HPV DNA (below 25 copy amplification le~el)-~Included HPV 16,18,33,35,39,51,52,55,56,58,11,40,42,53,54,57,unknown,clinical and undetermined types. results of the international study Bosch et al (1995)-P Three low-grade cases and 1 control with insufficient HPV DNA for testing were Infection with multiple types of HPV has been linked to a higher risk of cervical neoplasia than that with a single-type infection (Morrison et al, 1991), although the prevalence of multiple-type infection among Low-grade ( 9 4 5 % ) and highgrade (7-33%) cases has varied among studies (Schiffman et al, 1993;Burmer et al, 1990;Lungu et al, 1992). In our study, the unequivocally higher ORs associated with high-risk type HPV regardless of the number of HPV types present suggest that one high-risk type HPV may be sufficient to transform the host cell and cause malignant changes (Bedell et al, 1989). When high-risk type HPV was absent, there was a large increase in risk associated with multiple-type infection in high-grade cases, raising the possibility that multiple-type infection may synergistically enhance the neoplastic process among women with low-risk HPV (Morrison et al, 1991), although this conclusion is based on small numbers.…”

Section: Discussionmentioning

confidence: 48%

Human papillomavirus and cervical neoplasia: A case‐control study in Taiwan

Liaw

Hsing

Chen

et al. 1995

Intl Journal of Cancer

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Multiple sexual partners and early age at first intercourse have been identified as major risk factors for cervical cancer in earlier epidemiologic studies (Brinton, 1992), implying that sexually transmitted agents might be involved in its etiology. Over the last decade, mounting evidence from laboratory (zur Hausen, 1994) and epidemiologic (Muiioz et al., 1992; Peng et aZ., 1991) studies has shown that sexually transmitted infection with genital types of human papillomavirus (HPV) may be the primary causal agent for cervical cancer worldwide (Bosch et al., 1995). However, the relationship between HPV and cervical intraepithelial neoplasia (CIN) is less well established. Among epidemiologic studies investigating this relationship, few (Schiffman et al., 1993;Bosch et al., 1993;Morrison et al., 1991) have been able to use HPV DNA testing methods with high sensitivity and broad type range (Schiffman, 1992a;Burmer et al., 1990). In particular, epidemiologic studies investigating the relationship of HPV with CIN have been quite limited in Asia, even though cervical cancer is the most common cancer among women in this region (Parkin et al., 1992).Cervical cancer is the leading cancer among women in Taiwan (31% of all incident cancers in women) with an annual age-adjusted incidence rate of 33.5 per 100,000 (Cancer Registry Annual Report in Taiwan Area, 1986), which is about 4 times higher than that in the United States (8.7 per 100,000) (Miller et al., 1993). Reasons for the high risk in Taiwan are unclear, since the reported prevalence of known epidemiologic risk factors for cervical cancer, in particular multiple sexual partners, is quite low compared with Western women (Schiffman et al., 1993;Bosch et al., 1993;Morrison et al., 1991;Shen et al., 1993). However, approximately 90% of the women in Taiwan have never had a Papanicolaou (Pap) smear (Health Annual Report in Taiwan Area, 1993), which might be related to the high risk.As reported in Western countries (Bosch et al., 1995), a clinical report from China and Taiwan has shown that HPV could be detected in over 70% of cervical cancer patients (Pa0 et al., 1993), suggesting that HPV may be an important risk factor for cervical cancer in this monogamous female population. To investigate the role of HPV and other possible etiologic factors in the full spectrum of cervical neoplasia in Taiwan, we conducted a case-control study as part of a community-based cervical neoplasia screening study, using a sensitive HPV testing method that detects a broad range of HPV types (Manos et al., 1989). METHODS Study population (screened women)In 1991, a community-based cervical neoplasia screening study was conducted among women aged 30-64 in 4 rural townships in Taiwan with high cancer mortality rates. Women who had never been married or who had a history of cervical neoplasia or a hysterectomy were ineligible for the screening. As of June, 1992, 5,286 women had been recruited into the screening study. Briefly, at screening, Pap smears and cervigrams, magnified photographic imag...

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Section: Discussionmentioning

confidence: 48%

Human papillomavirus and cervical neoplasia: A case‐control study in Taiwan

Liaw

Hsing

Chen

et al. 1995

Intl Journal of Cancer

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“…pSGl6E6, pSG16E6A106-110 and pSG16E6YYH plasmids were constructed by inserting the BamHI fragment from plasmids pJ4Q 16E6, pJ4Q 16E6A106-110 and pJ4Q 16E6TYR/TYR/HIS45/47/49 (Crook et al,199 la) respectively into the BamHI site of pSG5. The plasmids pC53-SN3 , pC53-SCX3 , PCNAcat (Morris and Mathews, 1991), pRasCATI (Ishii et al, 1985), pfos363 (Gius et al, 1990), pJYM (Lusky and Botchan, 1981) and pl8MTE6 (Bedell et al, 1989) have been described previously.…”

Section: Plasmidsmentioning

confidence: 99%

“…Total RNA was isolated and 10 tcg hybridized in RNA (Northern) blots as described by Bedell et al (1989). All Northern blots were stripped and reprobed with the glyceraldehyde-3-phosphate dehydrogenase gene to confirm equal loading of RNA.…”

Section: Northern and Western Blot Analysesmentioning

confidence: 99%

Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription.

et al. 1992

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The transforming proteins of DNA tumor viruses SV40, adenovirus and human papillomaviruses (HPV) bind the retinoblastoma and p53 cell cycle regulatory proteins. While the binding of SV40 large T antigen and the adenovirus E1B 55 kDa protein results in the stabilization of the p53 protein, the binding of HPV16 and 18 E6 results in enhanced degradation in vitro. To explore the effect of viral proteins on p53 stability in vivo, we have examined cell lines immortalized in tissue culture by HPV18 E6 and E7 or SV40 large T antigen, as well as cell lines derived from cervical neoplasias. The half‐life of the p53 protein in non‐transformed human foreskin keratinocytes in culture was found to be approximately 3 h while in cell lines immortalized by E6 and E7, p53 protein half‐lives ranged from 2.8 h to less than 1 h. Since equivalent levels of E6 were found in these cells, the range in p53 levels observed was not a result of variability in amounts of E6. In keratinocyte lines immortalized by E7 alone, the p53 half‐life was found to be similar to that in non‐transformed cells; however, it decreased to approximately 1 h following supertransfection of an E6 gene. These observations are consistent with an interaction of E6 and p53 in vivo resulting in reductions in the stability of p53 ranging between 2‐ and 4‐fold. We also observed that the expression of various TATA containing promoters was repressed in transient assays by co‐transfection with plasmids expressing the wild‐type p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The cloned DNAs of those HPV types which are associated with lesions that have a high risk for malignant progression encode cellular transformation properties in established rodent fibroblasts (Yasumoto et al, 1986), in primary rodent cells (Matlashewski et al, 1987;Phelps et al, 1988;Storey et al, 1988) and in primary human cells (Durst et al, 1987;Pirisi et al, 1987;Schlegel et al, 1988). Genetic analysis of HPV-16 and HPV-18 has revealed that the E7 gene of these viruses encodes an oncoprotein that is sufficient for the induction of focus formation of established rodent fibroblasts (Kanda et al, 1988;Phelps et al, 1988;Vousden et al, 1988;Watanabe and Yoshiike, 1988;Bedell et al, 1989;Tanaka et al, 1989). The HPV-16 E7 protein has been most extensively studied.…”

Section: Introductionmentioning

confidence: 99%

Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.

et al. 1989

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The E7 proteins encoded by the human papillomaviruses (HPVs) associated with anogenital lesions share significant amino acid sequence homology. The E7 proteins of these different HPVs were assessed for their ability to form complexes with the retinoblastoma tumor suppressor gene product (p105‐RB). Similar to the E7 protein of HPV‐16, the E7 proteins of HPV‐18, HBV‐6b and HPV‐11 were found to associate with p105‐RB in vitro. The E7 proteins of HPV types associated with a high risk of malignant progression (HPV‐16 and HPV‐18) formed complexes with p105‐RB with equal affinities. The E7 proteins encoded by HPV types 6b and 11, which are associated with clinical lesions with a lower risk for progression, bound to p105‐RB with lower affinities. The E7 protein of the bovine papillomavirus type 1 (BPV‐1), which does not share structural similarity in the amino terminal region with the HPV E7 proteins, was unable to form a detectable complex with p105‐RB. The amino acid sequences of the HPV‐16 E7 protein involved in complex formation with p105‐RB in vitro have been mapped. Only a portion of the sequences that are conserved between the HPV E7 proteins and AdE1A were necessary for association with p105‐RB. Furthermore, the HPV‐16 E7‐p105‐RB complex was detected in an HPV‐16‐transformed human keratinocyte cell line.

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Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells

Cited by 158 publications

References 45 publications

Human papillomavirus and cervical neoplasia: A case‐control study in Taiwan

Human papillomavirus and cervical neoplasia: A case‐control study in Taiwan

Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription.

Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.

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