p21(Waf1/Cipl) and p53 Protein Expression in Breast Cancer

Wakasugi, E; Kobayashi, Tetsuro; Tamaki, Yasuhiro; Ito, Yasuhiro; Miyashiro, Isao; Komoike, Yoshifumi; Takeda, Tsutomu; Shin, Eisei; Takatsuka, Yuichi; Kikkawa, Nobuteru; Monden, Takushi; Monden, Morito

doi:10.1093/ajcp/107.6.684

Cited by 78 publications

(68 citation statements)

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“…In breast carcinoma cases, an inverse expression of p21 and p53 proteins has been reported (18). Reduced immunohistochemical expression of p27 in breast carcinoma in comparison to benign lesions has also been reported (19).…”

Section: Discussionmentioning

confidence: 94%

Immunohistochemical Analysis of Ki-67, p53, p21, and p27 in Benign and Malignant Apocrine Lesions of the Breast: Its Correlation to Histologic Findings in 43 Cases

et al. 2000

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Section: Discussionmentioning

confidence: 94%

Immunohistochemical Analysis of Ki-67, p53, p21, and p27 in Benign and Malignant Apocrine Lesions of the Breast: Its Correlation to Histologic Findings in 43 Cases

et al. 2000

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“…In the previous studies with clinical material, p21 expression has correlated with tumour proliferation and differentiation either in a p53-dependent (Doglioni et al, 1996;Harada et al, 1997;Wakasugi et al, 1997) or in a p53-independent pathway (DiGiuseppe et al, 1995;Tron et al, 1996;Yasui et al, 1996;Nadal et al, 1997). So far, PCNAtot, PCNA expression in ten consecutive high power fields; p53 index, (% of p53-positive tumour cells) × (staining intensity of p53); *log-rank analysis.…”

Section: Discussionmentioning

confidence: 97%

p21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

et al. 1999

Br J Cancer

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Tumour suppressor p21 WAF1/CIP1 is the main downstream effector gene mediating p53-induced cell cycle arrest, up-regulated by normal wild-type p53 (El-Deiry et al, 1993). In addition to direct transcriptional induction by the tumour suppressor p53, various other signals can induce p21 expression in the absence of wildtype p53 (Michieli et al, 1994;Zeng and El-Deiry, 1996). Harper et al (1993) showed that the ability of the p21 gene product to arrest the cell cycle is based on its virtue to bind and inhibit active cyclin/CDK complexes needed in DNA replication and cell cycle progression. p21 can also inhibit DNA replication by directly binding to the proliferating cell nuclear antigen (PCNA) molecule, thus inhibiting the ability of DNA polymerase δ to extend new DNA chains but still allowing the DNA repair function to continue (Flores-Rozas et al, 1994;Waga et al, 1994;Podust et al, 1995).In human melanoma cell lines, induction of p21 is independent of wild-type p53 expression (Jiang et al, 1995;Vidal et al, 1995), and elevated expression of p21 is associated with melanoma differentiation, growth arrest and metastatic suppression (Jiang et al, 1995). However, the knowledge of p21 expression in clinical materials of cutaneous malignant melanoma is rather limited. Maelandsmo et al (1996) revealed a significant correlation between elevated p21 expression and increasing tumour thickness in superficially spreading melanoma, but no correlation between p21 and survival was found. Elsewhere, a significant overexpression of p21 has been demonstrated in primary and metastatic melanomas (Trotter et al, 1997).As far as the authors are aware, no previous study has compared the relationships between p21, p53 and PCNA expression in primary stage I cutaneous melanoma. In the present study, we used immunohistochemistry to analyse the above-mentioned relationships in a cohort of 369 patients with long-term follow-up data. In addition, our aim was to analyse whether p21 protein levels are related to clinical data, histological parameters (Clark and Breslow levels) and prognosis. MATERIALS AND METHODS PatientsThe retrospective study consists of a consecutive series of 369 clinical stage I cutaneous malignant melanoma patients with complete clinical and histopathological data available, who were diagnosed and treated in the district of Kuopio University Hospital, Finland, between 1974 and 1989. The clinical staging of all tumours was carried out according to UICC (UICC, 1987). Because of insufficient tumour material, pigment or technical artefacts, there were 267 valid immunostainings for p21, 284 for p53 and 219 for PCNA respectively. Patient records were reviewed and the pertinent clinical and histopathological data of the patients are shown in Table 1. The mean follow-up time of all 369 patients was 6.4 years (range 0.2-18 years). When the analysis was restricted to patients with p21, p53 or PCNA data, the mean follow-up times were 6.3 years (range 0.5-18 years), 6.3 years (range 0.5-18 years) or 7.2 years (range 0.5-18 years) re...

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“…RB, a cell cycle regulator, is also mutated in a small percentage of sporadic human breast cancers (Berns et al, 1995). In addition, p21/WAF1/ CIP1, a cyclin-dependent kinase inhibitor that regulates G1-S cell cycle progression, is downregulated in some breast tumors, especially those with poor prognosis (Jiang et al, 1997;Wakasugi et al, 1997).…”

Section: Collaboration Between Wnt-1 and Other Genes In Oncogenesismentioning

confidence: 99%

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

2000

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Wnt-1 was ®rst identi®ed as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse mammary tumor virus LTR enhancer causes extensive ductal hyperplasia early in life and mammary adenocarcinomas in approximately 50% of the female transgenic (TG) mice by 6 months of age. Metastasis to the lung and proximal lymph nodes is rare at the time tumors are detected but frequent after the removal of the primary neoplasm. The potent mitogenic e ect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an increased latency in estrogen receptor a-null mice. Several genetic lesions, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation of one allele of Rb do not a ect the rate of tumor formation in Wnt-1 TG mice.

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p21(Waf1/Cipl) and p53 Protein Expression in Breast Cancer

Cited by 78 publications

References 0 publications

Immunohistochemical Analysis of Ki-67, p53, p21, and p27 in Benign and Malignant Apocrine Lesions of the Breast: Its Correlation to Histologic Findings in 43 Cases

Immunohistochemical Analysis of Ki-67, p53, p21, and p27 in Benign and Malignant Apocrine Lesions of the Breast: Its Correlation to Histologic Findings in 43 Cases

p21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

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