Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes.

Abstract

The There is convincing epidemiological and experimental evidence linking specific types of human papillomavirus (HPV) with the etiology of cervical cancer (1, 2). HPV-16 and -18 are present in >70% of cervical dysplasias and carcinomas, whereas HPV-6 and -11 are usually found in benign genital condyloma acuminata (3, 4). The E6-E7 genes of HPV-16, which are expressed at high levels in cervical carcinomas, encode proteins that are capable of transcriptional regulation and cellular transformation through interactions with cellular proteins, such as the tumor suppressor gene products pRB and p53 (5). These functions suggest an important role of HPV-16 in the initiation of cervical cancers.The HPV-16 DNA is frequently found in metastases of cervical cancers in either local lymph nodes (6)(7)(8)(9)(10)(11)(12)(13)(14) or distant site (15). The same HPV DNA sequences are consistently detected in metastases and primary tumors from the same patients, suggesting the same origin of viral DNA, and in situ hybridization has demonstrated the HPV DNA within the nuclei of metastatic cells (9, 10). HPV-16 DNA can also be detected in histologically negative lymph nodes (8, 11), suggesting that it may provide a sensitive indicator for early metastases. It is not known, however, whether the expression of HPV genes influences the ability of a tumor to metastasize, and it is controversial whether human cervical cancers with HPV-16 DNA are more invasive than those associated with nononcogenic HPV types or HPV-negative cancers (16)(17)(18).To investigate the relationship between the expression of HPV-16 genes and tumor metastasis, we have assessed the ability of murine cell lines expressing the E6 and E7 genes from oncogenic HPV-16 or nononcogenic HPV-6b to formThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. metastasis in a nude mouse model. We report here that the expression in mouse cell lines of the E6 and E7 genes from HPV-16, but not from HPV-6b, results in metastatic conversion. MATERIALS AND METHODSMice. Female BALB/c (nu/nu) mice, 4-8 weeks old, and C3H/HeN mice, 6-8 weeks old, were bought from HarlanSprague-Dawley.Cell Lines. NCTC2555 is a fibrosarcoma line of C3H/HeN mouse origin (19), and the NIH 3T3 fibroblast line is BALB/c mouse origin. The CaSki line was derived from a HPV-16-positive squamous cell carcinoma of human cervix. PA317 and t-2 are packaging cell lines for amphotropic or ecotropic retroviruses, respectively. YAC-1 is a natural killer (NK) cell-sensitive lymphoma line and EL-4 is a NK-resistant lymphoma line. All cells were purchased from American Type Culture Collection and were maintained at 37°C with Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (HyClone) in a humidified atmosphere of 5% C02/95% air.Gene Transfer by Recombinant Retroviruses. Retroviruses were prepared as described (20,21) at biosafety level 2....

The Aetiological Role of Human Papillomavirus in Colorectal Carcinoma: An Iranian Population- Based Case Control Study

“…Therefore, this study supports the hypothesis that expresses the different frequency patterns of HPV infection according to geographical variations and ethnicity of the populations (Jung et al, 2004;Chansaenroj According to Table 3, analysis of medical data in infected patients with CRC in compare to non-infected patients with CRC explained a possible association between high-risk types of HPV infections and accession Gillison and shah (2003), Chen et al (2012), Hamid and Mustafa (2012), Ghasemian et al (2013), Zandberg et al (2013) in comparison with results from Motlagh et al (2007), Giuliani et al (2008) investigate the ability of HPV infection to induce advanced stages of cancer in different malignancies. Furthermore, this study highlights the impact of high-risk types of HPV infection in distant metastasis and malignant lymph nodes invasion in compare with non-infected patients, which have been previously reported in several investigations (Chen et al, 1993;Gillison and shah, 2003;Bognar et al, 2008;McHugh et al, 2009;Zandberg et al, 2013). Gillison and Shah (2003) indicated that HPV associated malignancies would occur at anatomic subsites of exposure by direct contact, since there is no viremic phase in the pathogenesis of HPV, so the infection is not widely disseminated in the body.…”

Low Surface Expression of B7-1 (CD80) Is an Immunoescape Mechanism of Colon Carcinoma

“…C51 and MC38 cells were transfected with a previously described recombinant retrovirus expressing murine b7-1 gene (3,45). Transfections were done by incubating supernatant of the packaging c-2 lines in the presence of polybrene as previously described (46). B7 + -transfected cells were positivelyselected by immunofluorescence-activated cell sorting (using an EPICS-C, Coulter, Fullerton, CA) and drug selection as previously described (3).…”

Effects of the NIK aly Mutation on NF-κB Activation by the Epstein-Barr Virus Latent Infection Membrane Protein, Lymphotoxin β Receptor, and CD40

“…Before initiating this series of experiments, the MEFs were first transformed with a human papilloma virus 16 E6 and E7-expressing retrovirus so as to enhance their growth and transfection efficiency (24). The surprising result was that LMP1, LMP1/LT␤R, and LMP1/CD40 activated NF-B similarly in wt and aly/aly MEFs indicating that NIK is not essential for NF-B activation by these receptors in fibroblasts (Fig.…”