Low Levels of p27 in Association With Deregulated p53-pRb Protein Status Enhance Tumor Proliferation and Chromosomal Instability in Non-Small Cell Lung Carcinomas

Tsoli, Efthymia; Gorgoulis, Vassilis G.; Zacharatos, Panayotis; Kotsinas, Athanassios; Mariatos, G.; Kastrinakis, Nikolaos G.; Kokotas, S.; Kanavaros, Panagiotis; Asimacopoulos, Panayiotis J.; Bramis, John; Kletsas, Dimitris; Papavassiliou, Athanasios G.; Kittas, Christos

doi:10.1007/bf03402188

Cited by 14 publications

(35 citation statements)

References 34 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Immunohistochemistry used to reveal Ki-67 protein was not always performed with the same antibody: clone Mib-1 in the majority of the studies (Costes et al, 1995;Bohm et al, 1996;Fontanini et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Minami et al, 2002;Rigau et al, 2002), antibodies coming from a firm selling several clones but without mention of the clone used (Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Giaccone et al, 1995;Pujol et al, 1996;Mehdi et al, 1998;Soomro et al, 1998;Carbognani et al, 2002); any mention of the antibodies used (Tungekar et al, 1991;Harpole Jr et al, 1995Giatromanolaki et al, 1996a, b;D'Amico et al, 1999D'Amico et al, , 2000Carvalho et al, 2000;Pelosi et al, 2001)…”

Section: Discussionmentioning

confidence: 99%

“…In total, 42 studies published between 1991 and 2002 were selected for this systematic review (Tungekar et al, 1991;Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Costes et al, 1995;Giaccone et al, 1995;Harpole, Jr et al, 1995Bohm et al, 1996;Fontanini et al, 1996;Giatromanolaki et al, 1996a, b;Pujol et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Mehdi et al, 1998;Soomro et al, 1998;D'Amico et al, 1999D'Amico et al, , 2000Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Carvalho et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Pelosi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Carbognani et al, 2002;Minami et al, 2002;Rigau et al, 2002). Five were excluded because an identical patients cohort was used in another selected publication (references excluded/includ...…”

Section: Studies Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

View full text Add to dashboard Cite

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30 -1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

View full text Add to dashboard Cite

show abstract

“…7,8 Reduced p57 KIP2 expression in certain tumors [9][10][11][12] is inversely associated with cellular proliferation, suggesting an oncosuppressor activity, whereas in others p57 KIP2 expression is positively correlated with proliferation indicating an opposite function. 13 In childhood tumors, contradictory p57 KIP2 expression results have also been reported.…”

Section: Low P27mentioning

confidence: 99%

“…Of the 70 employed cases, 10 patients have been previously examined for p27 KIP1 expression status, proliferation and apoptotic indexes. 7 Patients received no chemo-, radio-or immunotherapy prior to surgery. The study was performed following criteria of the revised (1983) Helsinki Declaration of 1975.…”

Section: Tissue Samplesmentioning

confidence: 99%

Downregulation of the KIP family members p27^KIP1 and p57^KIP2 by SKP2 and the role of methylation in p57^KIP2 inactivation in nonsmall cell lung cancer

Pateras

Apostolopoulou

Koutsami

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Knowing the status of molecules involved in cell cycle control in cancer is vital for therapeutic approaches aiming at their restoration. The p27 KIP1 and p57 KIP2 cyclin-dependent kinase inhibitors are nodal factors controlling normal cell cycle. Their expression in normal lung raises the question whether they have a mutual exclusive or redundant role in nonsmall cell lung cancer (NSCLC). A comparative comprehensive analysis was performed in a series of 70 NSCLCs. The majority of cases showed significantly reduced expression of both members compared to normal counterparts. Low KIP protein levels correlated with increased proliferation, which seems to be histological subtype preponderant. At mechanistic level, degradation by SKP2 was demonstrated, in vivo and in vitro, by siRNA-methodology, to be the most important downregulating mechanism of both KIPs in NSCLC. Decreased p57 ), suggested that inhibition of the SKP2-degradation mechanism restores p27 KIP1 and p57 KIP2 expression. Double siRNA treatments demonstrated that each KIP is independently capable of restraining cell growth. An additional demethylation step is required for complete reconstitution of p57 KIP2 expression in NSCLC. ' 2006 Wiley-Liss, Inc.

show abstract

“…Ki-67 index (KI) was used as a comparative measure for the level of Ki-67 expression among different tissue sections. KI estimated as the percentage obtained from the number of Ki-67 positively stained glandular cells over total glandular cells in 7-10 high power fields (total counted cells: about 1000) [39] .…”

Section: Methodsmentioning

confidence: 99%

The Interplay between p53 and p21 Tumor Suppressor Proteins in the Transformation of Colorectal Adenoma to Carcinoma

Abdulamir¹,

Hafidh²,

Mahdi³

et al. 2008

American J. of Immunology

View full text Add to dashboard Cite

This study was carried out for evaluating the interplay of p53, p21 and Ki-67 proteins along the colorectal adenoma-carcinoma oncogenic transformation sequel. Therefore, Fifty colorectal cancer and 14 adenoma patients were involved. The histopathological expression of p53, p21 and Ki-67 proteins was evaluated by immunohistochemistry assay. The results revealed that remarkable overexpression of p53 protein was seen in the tumorous sections of cancer patients more than that in adenoma patients (p<0.05), while no p53 overexpression was found in the corresponding nontumorous sections. The positive expression of p21 protein was lower in the tumorous sections of cancer patients than that of adenoma patients (p<0.05) and was higher in the non-tumorous than the corresponding tumorous sections of both CRC and adenoma patients (p<0.05). The expression of p53 and p21 proteins in cancer patients was inversely correlated to each other (p<0.05) and the expression of p21 rather than p53 protein was associated with colorectal cancer staging and grading (p<0.05). Ki-67 was higher in cancer than in adenoma patients and higher in the tumorous tissue sections than the corresponding non-tumorous sections (p<0.05). The overexpression of p53 and downexpression of p21 proteins in colorectal cancer might be responsible largely for triggering the transformational changes in normal mucosa to develop adenoma and trigger also the malignant cascade from adenoma to carcinoma. P53 overexpression was shown to occur due to the mutated dysfunctional p53 gene product which loses its transcriptional activator necessary for p21 expression. The level of p21 protein which is a quantitatively affected by the loss of p53 activation is responsible for the association with cancer staging and grading that serves as a good indicator for the disease progression.

show abstract

Low Levels of p27 in Association With Deregulated p53-pRb Protein Status Enhance Tumor Proliferation and Chromosomal Instability in Non-Small Cell Lung Carcinomas

Cited by 14 publications

References 34 publications

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Downregulation of the KIP family members p27^KIP1 and p57^KIP2 by SKP2 and the role of methylation in p57^KIP2 inactivation in nonsmall cell lung cancer

The Interplay between p53 and p21 Tumor Suppressor Proteins in the Transformation of Colorectal Adenoma to Carcinoma

Contact Info

Product

Resources

About

Low Levels of p27 in Association With Deregulated p53-pRb Protein Status Enhance Tumor Proliferation and Chromosomal Instability in Non-Small Cell Lung Carcinomas

Cited by 14 publications

References 34 publications

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Downregulation of the KIP family members p27KIP1 and p57KIP2 by SKP2 and the role of methylation in p57KIP2 inactivation in nonsmall cell lung cancer

The Interplay between p53 and p21 Tumor Suppressor Proteins in the Transformation of Colorectal Adenoma to Carcinoma

Contact Info

Product

Resources

About

Downregulation of the KIP family members p27^KIP1 and p57^KIP2 by SKP2 and the role of methylation in p57^KIP2 inactivation in nonsmall cell lung cancer