Up-regulation of hormone response of human papillomavirus type 16 expression and increased DNA-protein binding by consensus mutations of viral glucocorticoid response elements

Khare, Satya Rashi; Kumar, Kotlo U.; Tang, Shou Ching; Pater, Mary M.; Pater, Alan

doi:10.1002/(sici)1096-9071(199611)50:3<254::aid-jmv8>3.0.co;2-8

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…Glucocorticoids in particular, such as the synthetic glucocorticoid dex, have been shown to enhance the transformation rate of highrisk HPV-transfected cells (16,44,54), suggesting the oncogenic potential of glucocorticoids in conjunction with HPV. GREs have been identified in the URRs of HPV11, HPV16, and HPV18 and have been suggested in others, including that of HPV31 (7,9,11,20,31,40,44,72). In the present study we attempted to show dex inducibility of the HPV31 URR.…”

Section: Discussionmentioning

confidence: 74%

“…It has always been assumed that, like HPV16 and HPV18 (7,9,12,20,31,40), HPV31 contains GREs in its URR (9). In fact, in the published report of the HPV31 sequence, a potential GRE is highlighted as being present in the URR (22).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the cellular and viral factors mentioned that bind the URR of HPV, glucocorticoid response elements (GREs) have also been identified in the URRs of several HPV types, including HPV11, HPV16, and HPV18 (7,9,20,31,44,56,72). Furthermore, the presence of GREs has been pro-posed in the URRs of HPV6, HPV31, and HPV33 (9).…”

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confidence: 99%

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The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction

Bromberg-White

Meyers

2002

J Virol

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The upstream regulatory region (URR) of various types of human papillomaviruses (HPVs) has been shown to contain functional glucocorticoid response elements (GREs), including HPV type 11 (HPV11), HPV16, and HPV18. Glucocorticoids have been demonstrated to induce the transcriptional activity of the early promoters of these HPV types. Although it has been assumed that the URR of HPV31 contains at least one GRE, no functionality has been demonstrated. We attempt to show here inducibility of the URR of HPV31 by the synthetic glucocorticoid dexamethasone (dex). By sequence analysis we identified three potential GREs in the URR of HPV31. Gel shift analysis indicated that each of these three sites has the potential to be a functional GRE. However, constructs containing the full-length URR, 5 deletions of the URR, and an internal fragment of the URR containing all three putative GREs were only weakly inducible by dex. Linker scanning mutants, whereby each potential GRE was replaced individually, in double combination, or in triple combination by a unique polylinker, had no effect on dex inducibility. Replacement of each of the three HPV31 GREs with the GRE of HPV18 failed to induce a response to dex. Placement of the HPV18 GRE into the URR of HPV31 in a region similar to its location in the HPV18 URR was also unable to result in a strong dex induction of the HPV31 URR. These data suggest that the lack of dex inducibility is due to the overall context of the HPV31 URR and may be dependent on the requirements of the major early promoter for transcriptional activation. Human papillomaviruses (HPVs) are small, doublestranded DNA viruses that specifically infect mucosal and cutaneous epithelium. Over 100 types of HPV have been identified, with roughly one-third infecting the genital epithelium. With the identification of HPV as the etiologic agent of cervical cancer (74, 76), HPV types that infect the genital epithelium are separated based on their associated risk. High-risk types, most commonly HPV type 16 (HPV16) and HPV18, are frequently found in high-grade cervical lesions and invasive cancer. Intermediate-risk types, including HPV31, HPV33, and HPV35, are associated with all grades of cervical lesions and are often associated with invasive cancer. Low-risk HPV types, most frequently HPV6 and HPV11, are commonly associated with low-grade cervical lesions and are rarely found in invasive cancer (35).The genomes of all of the genital HPV types are approximately 8 kb in length and are similarly organized into early, late, and noncoding regions. The noncoding region, or upstream regulatory region (URR), contains cis-enhancer elements to many cellular and viral factors. Binding of these factors to the URR modulates both viral replication and viral gene transcription (33). Binding sites have been identified for the viral proteins E1 and E2 (39,56,66,68), as well as for the cellular factors AP1 (12,25,30,34), Oct-1 (25), YY1 (30), Sp1 (25), NF1 (21), TEF-1 (30), and CDP/Cut (48, 55), among others.Steroid hormones have been sugg...

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Section: Discussionmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

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The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction

Bromberg-White

Meyers

2002

J Virol

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“…The products of the four genes have different transactivation abilities and generate heterodimers with intermediate activation potentials (61). Stimulations of the human papillomavirus type 16 and aspartate aminotransferase promoters by glucocorticoid require the presence of intact NF1-binding sites (62,63). The glucocorticoid receptor favors binding of CTF/NF1 factors to the murine mammary tumor virus promoter in vivo by stimulating the nucleosome disrupting activity of the SWI/SNF complex (64).…”

Section: -Iia Promoter Is Critical For the Stimulation Of Its Activitmentioning

confidence: 99%

Induction of Secreted Type IIA Phospholipase A2 Gene Transcription by Interleukin-1β

Massaad

Paradon

Jacques

et al. 2000

Journal of Biological Chemistry

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The synovial fluid of patients suffering from rheumatoid arthritis or osteoarthritis contains large quantities of prostaglandin E2. Such quantities inhibit collagen synthesis and therefore contribute to joint destruction. These inflammatory lipid mediators are produced by a cascade of enzymes among which phospholipases A 2 (PLA 2 ) 1 play a key role by releasing arachidonic acid from membrane phospholipids. Two calciumdependent PLA 2 are involved in the release of arachidonic acid. Cytosolic PLA 2 , a ubiquitous 85-kDa enzyme, is activated by MAP kinases and translocated from the cytosol to membrane (1, 2). Type IIA secreted PLA 2 (sPLA 2 -IIA) was originally purified from the synovial fluid of patients with rheumatoid arthritis, which contains high quantities of this enzyme (3). sPLA 2 -IIA belongs to a large group of 13-15-kDa secreted enzymes present in mammalian fluids and in the venoms of snakes and insects. According to a recent classification (4), the pancreatic version of the enzyme has been included in a type I group whereas the synovial PLA 2 is referred as type IIA sPLA 2 . Three other recently cloned mammalian PLA 2 were classified in IIC, V, and X groups, but their involvement in the arachidonic acid release remains unknown. Purified or recombinant sPLA 2 -IIA triggers joint inflammation when it is injected intra-articularly in rabbits (5). The number of rheumatoid arthritis-affected joints and the presence of destructive erosion have been correlated with the amount of sPLA 2 -type IIA in the serum of patients (6). Mice with both the TNF␣ and sPLA 2 -IIA transgenes exhibit more joint destruction than do those with TNF␣ alone (7). Interleukin-1␤ (IL-1␤) is the most abundant cytokine in inflammatory synovial fluids. It stimulates the expression of numerous genes in articular cells (8) and increases the level of sPLA 2 -IIA mRNA in chondrocytes. We have previously demonstrated that prostaglandin E2 production by rabbit articular chondrocytes is related to plasma membraneassociated sPLA 2 -IIA activity and that the transcription rate of sPLA 2 -IIA gene is stimulated by IL-1␤ (9 -11).Three main classes of transcriptional factors have been shown to mediate the effect of IL-1␤ on gene transcription: (i) NF-B is a dimer of p50 and p65 subunits and belongs to the Rel family. (ii) A member of the STAT family of transcription factors, which are activated through phosphorylation by Jak kinases and translocated to the cell nucleus within a few minutes, was characterized as an IL-1␤-stimulated factor but can also be activated by IL-6 and lipopolysaccharide (12). (iii) AP-1 can also be involved in the IL-1␤ pathway because IL-1␤ induces the transcription of the c-Jun and c-Fos genes in some cell models (13).C/EBP transcription factors are involved in the regulation of gene transcription by IL-6. The C/EBP family includes three main members: C/EBP␣, C/EBP␤, and C/EPB␦. This last member is transcriptionally induced by 15), whereas C/EBP␤ is mainly regulated at the post-transcriptional level by this cytokine in hepa...

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“…At least 3 GREs respond to both progesterones and glucocorticoids by increasing the transcription of the E6 and E7 genes of the high‐risk types HPV‐16 and HPV‐18 and the low‐risk type HPV‐11 11, 12, 13, 14. This response depends on the activity of other binding sites, e.g., NF‐1 and AP1, positioned in the same region of the LCR as the GRE;15, 16 and a complex interaction of c‐jun and c‐fos and the glucocorticoid receptor with the HPV‐16 GRE has been demonstrated 17. Interestingly, not all HPV GREs respond to hormones to the same degree.…”

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confidence: 99%

Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma

Villiers

2002

Intl Journal of Cancer

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Available data demonstrate an increase in the transcription of high-risk papillomaviruses by the 16␣-hydroxylation of estrogens, which is in line with the epidemiologic data showing an increased cervical carcinogenesis risk for long-term contraceptive-using, HPV-infected women. No evidence exists for an increase in HPV-negative contraceptive users. © 2002 Wiley-Liss, Inc. Key words: HPV; hormone; cervical intraepithelial neoplasia; cervical cancerInfection by papillomaviruses is essential for the development of cervical cancer (reviewed by zur Hausen 1 ). A number of the papillomavirus types (high-risk) have been associated with and demonstrated in premalignant and malignant lesions of the genital tract. The infection per se is, however, not sufficient to induce malignant conversion. A complex interplay between viral and cellular genes is required to disrupt the cell-cycle control and induce immortalization, followed by progression to malignant conversion. The molecular mechanism through which papillomaviruses, in particular HPV-16 and HPV-18, participate to achieve this condition has been well established. The low-risk mucosal papillomaviruses, causing benign lesions mainly of the genital tract, share several functional characteristics with the high-risk mucosal papillomaviruses but lack others necessary for the immortalization of normal keratinocytes (reviewed by zur Hausen 2 ). The maintenance of a high level of certain viral proteins within the cell is necessary for the virus to induce and regulate distinct cellular pathways. Several exogenous and endogenous factors controlling or influencing viral transcription and the expression of the viral oncogenes, E6 and E7 in particular, are known. Very few data are available on the in vitro and in vivo mechanisms through which steroid hormones, in particular, influence the carcinogenic process induced by high-risk papillomavirus infections.Steroid hormones exert a broad range of biologic functions. The synthesis, transport and metabolism of the naturally occurring hormones are tightly regulated in various organs of the body (reviewed by Clemens and Goss 3 and Gruber et al. 4 ). A delicate balance exists during the premenstrual, menstrual and postmenopausal phases of the female body, as well as during pregnancy. This balance is greatly influenced by the intake of exogenous steroid hormones in the form of OCs in young women or HRT in postmenopausal women. Reports in which epidemiologic data taken from 8 case-control studies have been pooled and analyzed indicate an increased risk for developing cervical carcinoma in women with high parity 5 or after the long-term use of OCs. 6 Odds ratios were 3.8 for cervical carcinoma after 7 full-term pregnancies, and 2.3 for women with 1 or 2 full-term pregnancies, respectively. Odds ratios for use of OCs were 2.82 for 5-to 9-year use and 4.03 for 10-year or longer use. Other epidemiologic studies have also reported an increased risk of developing cervical adenocarcinoma among long-term users of OCs. [7][8][9] Regulation of viral ...

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Up-regulation of hormone response of human papillomavirus type 16 expression and increased DNA-protein binding by consensus mutations of viral glucocorticoid response elements

Cited by 10 publications

References 39 publications

The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction

The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction

Induction of Secreted Type IIA Phospholipase A2 Gene Transcription by Interleukin-1β

Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma

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