Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines

Min, Byung‐Moo; Baek, Jeong‐Hwa; Shin, Kihyuk; Gujuluva, Chandrasekhar; Cherrick, Henry M.; Park, No-Hee

doi:10.1016/0964-1955(94)90036-1

Cited by 95 publications

(73 citation statements)

References 22 publications

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“…The p53 pathway in the SCC lines investigated here has previously been analysed and all of the lines showed evidence for non-functional p53 (Burns et al, 1993;Min et al, 1994;S Timmermann and K MuÈ nger, unpublished). 5-Aza-CdR treatment restored the pRB pathway in SCC cells by re-expressing p16 ink4a protein.…”

Section: Discussionmentioning

confidence: 82%

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2′-deoxycytidine treatment induces a senescence-like state

1998

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We have previously reported that a set of oral squamous cell carcinoma lines express speci®cally elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 ampli®cation and expresses functional p16 ink4a , the other cell lines express undetectable levels of p16 ink4a , despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16 ink4A promoter and a third cell line, SCC9, has a mutation in the p16 ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16 ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16 ink4a . In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16 ink4a persisted, even after the drug was removed and the cells expressed senescence-associated b-galactosidase activity. Ectopic expression of p16 ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16 ink4a in response to treatment with a demethylating agent.

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Section: Discussionmentioning

confidence: 82%

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2′-deoxycytidine treatment induces a senescence-like state

1998

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“…If such is the case, ethanol should not induce a cell cycle delay in cells which do not express p53. To investigate this possibility, we compared the e ect of ethanol on the cell cycle progression in secondary NHOK expressing wild-type p53 and in the SCC-9 oral cancer cell line which does not express p53 (Min et al, 1994). As found with the RKO cells, a 16 h ethanol exposure induced an increase in the percentage of cells in G 1 in both the NHOK and SCC-9 cells (Figure 2b and c).…”

Section: Ethanol Prolongs the G 1 Phase Of The Cells Cyclementioning

confidence: 81%

“…The oral cancer cell lines SCC-4 and SCC-9 were cultured in DMEM/F12 medium (GIBCO/BRL) supplemented with 10% fetal bovine serum and 0.4 mg/ml of hydrocortisone. NHOK and RKO cells express wild-type p53 (Kuerbitz et al, 1992;Park et al, 1991), whereas the SCC-4 and SCC-9 cancer cells express mutant p53 and no p53, respectively (Min et al, 1994).…”

Section: Cell Culturementioning

confidence: 99%

Ethanol upregulates the expression of p21WAF1/CIP1 and prolongs G1 transition via a p53-independent pathway in human epithelial cells

1997

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The control of cell cycle progression is necessary for accuracy in the replication of DNA and the distribution of genetic information to daughter cells. Disturbances in progression of the cell cycle may result in the loss of genomic integrity, a`hallmark' of cancer cells. Extensive consumption of alcoholic beverages is a risk factor associated with the development of various human epidermoid cancer including oral and pharyngeal squamous cell carcinomas. However, e ects of ethanol on cell cycle progression and on the expression of genes associated with the cell cycle have not been studied. We report here that exposure of human epithelial cells to ethanol, at concentrations (100 ± 200 mM) that do not cause cell death, (a) does not a ect or only reduces slightly the cellular level of p53 protein, (b) upregulates the transcription of the WAF1/CIP1 gene, (c) inhibits the Cdk2 activity, and (d) reduces the rate of cellular proliferation by inducing a delay in G 1 phase transition. The results also indicate that, at these non-cytotoxic concentrations, ethanol exhibits its e ects through a p53-independent mechanism.

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“…34 In particular, with regard to viral involvement, it is still highly controversial whether HR HPV can be considered an etiologic or a malignant risk factor in oral carcinogenesis: 14 some research groups 14,35,36 have identified HR HPV antigens and viral DNA in potentially malignant and malignant oral lesions, and others have defined HR HPV as playing an important role in OSCC, especially in the absence of common oral habits. 37 Historically, evidence of the carcinogenic role of HR HPVs is based on 2 oncoproteins: HPV-E6, which promotes degradation of the p53 tumor-suppressor gene product, 38 and HPV-E7, which modifies pRb tumor-suppressor gene product function, leading to increased cell proliferation and contributing to carcinogenesis. 39,40 In a review on epidemiologic and molecular bases, Ha and Califano 41 attrib- uted to HR HPV a role in oral carcinogenesis but only in a small subset of cases, with differences reported in clinical outcome, response to radiotherapy and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Muzio

D’Angelo

Procaccini

et al. 2005

Intl Journal of Cancer

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Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered ( p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects ( p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPVpositive OSCC [root mean-square error (RMSE) = 5.89 3 10 -6 , % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; survivin; oral squamous cell carcinoma; fuzzy neural network; carcinogenesis OSCC is rapidly increasing in incidence and represents the most frequent malignant oral tumor. The incidence of metastasis depends on the degree of cellular differentiation, deep invasion and site of the primary tumor; however, outcome is difficult to predict if only standard clinicopathologic parameters are taken into account. Biologic markers that can help to identify lesions with an aggressive phenotype and worse prognosis need to be identified.Since the majority of human neoplasms are characterized by an imbalance of the regulatory cell cycle control processes, the study of OSCC using the expression of proteins involved in the critical checkpoints of cell apoptosis and growth starts by elucidating the processes of carcinogenesis and appears to have good prognostic value. 1 Indeed, we know that apoptosis, or programmed cell death, and its suppression are involved in the carcinogenesis of several tumors; this process, mediated by caspases and cysteine proteinases present as proenzymes, is inhibited by several proteins, such as those of the Bcl-2 and IAP families. Survivin is an IAP protein, which is abundantly expressed in most solid and hematologic malignancies but undetectable in ...

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Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines

Cited by 95 publications

References 22 publications

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2′-deoxycytidine treatment induces a senescence-like state

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2′-deoxycytidine treatment induces a senescence-like state

Ethanol upregulates the expression of p21WAF1/CIP1 and prolongs G1 transition via a p53-independent pathway in human epithelial cells

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

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