Frequent and heterogenous expression of cyclin-dependent kinase inhibitor WAF1/p21 protein and mRNA in urothelial carcinoma

Clasen, S.; Schulz, Wolfgang A.; Gerharz, C. D.; Grimm, Marc-Oliver; Christoph, Frank; Schmitz‐Dräger, Bernd J.

doi:10.1038/bjc.1998.84

Cited by 38 publications

(33 citation statements)

References 30 publications

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“…In our study, p21 staining did not correlate with tumour grade, which is in accordance with several recent observations in different neoplasms Slebos et al, 1996;Byrne et al, 1997). Overexpression of p21 has also been observed in low-grade (IÐII) urothelial tumours (Clasen et al, 1998). In addition, Doglioni et al (1996), Wang et al (1997) and Yasui et al (1997) described higher p21 expression in stages 0Ð2 colon carcinomas than in stages 3 and 4 carcinomas.…”

Section: Discussionsupporting

confidence: 80%

“…In addition, Doglioni et al (1996), Wang et al (1997) and Yasui et al (1997) described higher p21 expression in stages 0Ð2 colon carcinomas than in stages 3 and 4 carcinomas. There is also evidence supporting the hypothesis that p21 may exert its tumour suppressive effects in the early stages of tumour development (Ogawa et al, 1997;Clasen et al, 1998) to which the present study gives further strengthening. However, some cancer studies have not revealed any association between tumour stage and p21 expression (Slebos et al, 1996;Byrne et al, 1997;Bennet et al, 1998).…”

Section: Discussionsupporting

confidence: 62%

“…In colorectal and urothelial cancers, p21 expression has been reported to be heterogeneous and decreased compared to normal tissue Sasaki et al, 1996;Clasen et al, 1998). The majority (75%) of the tumours in our study showed p21 positivity, and 43% expressed p21 moderately or strongly.…”

Section: Discussionmentioning

confidence: 53%

“…This kind of phenomenon (independent and dependent mechanisms) has also been observed by Yasui et al (1997) in their series of colorectal tumours. In addition, previous studies on endometrial (Backe et al, 1997;Ito et al, 1997), ovarian (Werness et al, 1997) and urothelial carcinoma (Clasen et al, 1998) have failed to show a correlation between p21 expression and p53. The significance of intratumoural p21 and p53 staining heterogeneity can be hypothesized as follows: a population of cancer cells with one functional copy of p53 might still be able to activate p21 within a tumour in which the other cells have already lost both functional copies.…”

Section: Discussionmentioning

confidence: 97%

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p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis

et al. 1999

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p21/WAF1 expression was studied in a series of 162 colorectal carcinoma patients and its relation to p53- and activator protein (AP)-2 expressions and to stage as well as survival was assessed. p21 expression was moderate or intense in 33% of the tumours, and 53% of the tumours had moderate or strong p53 staining intensity. Eighty-nine percent of the tumours showed a weak cytoplasmic AP-2 signal. As expected, p21 and p53 stainings were inversely related to each other ( P < 0.001). There was a significant positive association between p21 and AP-2 expression levels ( P = 0.01). p21 intensity and percentage were higher in Dukes' A and B stages ( P < 0.001). The cancer-related survival and recurrence-free survival (RFS) rates were significantly lower among patients with a low signal for p21 ( P < 0.001) and low p21 percentage in tumour epithelium ( P < 0.001). High p53 staining intensity in tumour epithelium predicted poor survival ( P = 0.01) and RFS ( P = 0.003). In the multivariate analysis, p21 percentage distribution independently predicted cancer-related survival in all cases, and p21 expression intensity in T1–4/N0–3/M0 and T1–3/N0/M0 cases. p21 percentage distribution was an independent predictor of RFS in all and T1–3/ N0/M0 cases. AP-2 staining did not reach any prognostic significance. These results suggest that the immunohistochemical detection of cyclin-dependent kinase inhibitor p21 could be used to predict more precisely the outcome of colorectal cancer patients. © 1999 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 97%

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p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis

et al. 1999

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“…Quantitative analysis of mRNA levels was performed essentially as described (Clasen et al, 1998;Oya et al, 1998). Primer sequences and amplification conditions are listed in Table 2.…”

Section: Reverse Transcription and Pcrmentioning

confidence: 99%

Decreased expression of p57KIP2 mRNA in human bladder cancer

Oya

Schulz

2000

Br J Cancer

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Summary To identify targets of genetic and epigenetic alterations on chromosome 11p15.5 in human bladder cancer, expression of the imprinted KIP2, IGF2 and H19 genes was studied by quantitative RT-PCR in 24 paired samples of urothelial carcinomas and morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma cell lines. The most frequent alteration in tumour tissue was decreased expression of KIP2 identified in 9/24 (37%) specimens. Decreased IGF2 and H19 mRNA levels were found in five (21%) and three (13%) tumours, respectively. One tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found associated with loss of KIP2 expression, whereas decreased expression of IGF2 mRNA occurred independently. Almost all bladder carcinoma cell lines showed significant changes in the expression of at least one gene with diminished expression of KIP2 mRNA as the most frequent alteration. IGF2 mRNA levels were diminished in several lines, but increased in others. The KIP2 gene could be an important target of genetic and epigenetic alterations in bladder cancer affecting the maternal chromosome 11p15.5. However, reminiscent of the situation in Wilms' tumours, expression of the IGF2 gene on the paternal chromosome can also be disturbed in bladder cancers.

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Overexpression of p21 protein in radiation- transformed mouse 10T� cell clones

Krolewski

Little

2000

Mol. Carcinog.

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In order to investigate the hypothesis that aberrant expression of cell-cycle regulatory proteins may represent early events in the process of carcinogenesis, levels of expression of the negative regulators p21(waf1/cip1) (p21), p27(kip1) (p27), and p16(ink4a) (p16) and/or the positive regulators cyclin D(1) and cyclin E were examined by western blot analysis in cells transformed in vitro by ionizing radiation. The levels of these proteins in 12 independently derived mouse 10T(1/2) cell clones transformed by 1.5 Gy of alpha radiation were compared with those in nine similarly derived nontransformed control clones. Constitutive levels of p21 were very low in all control clones, whereas p21 expression was significantly elevated in nine of 12 transformed clones. Two of the three transformed clones displaying low levels of p21 expressed increased levels of p53. p21 regulation was also altered in response to radiation in transformed clones as compared with controls, only minimal induction was observed 4 h following gamma irradiation. Western blot analysis indicated a constant expression of p27 protein but slightly decreased levels of p16 in these transformed clones. Cyclin D(1) was overexpressed in 11 of 12 transformed clones; in only two of these were the levels of cyclin E elevated. Overall, the results suggest that alterations in the expression of cell cycle regulatory proteins may represent important events in radiation-induced oncogenic transformation in vitro. Although the specific alterations vary among different transformed clones, overexpression and aberrant regulation of p21 appear to be the most frequent ones.

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Frequent and heterogenous expression of cyclin-dependent kinase inhibitor WAF1/p21 protein and mRNA in urothelial carcinoma

Cited by 38 publications

References 30 publications

p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis

p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis

Decreased expression of p57KIP2 mRNA in human bladder cancer

Overexpression of p21 protein in radiation- transformed mouse 10T� cell clones

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