Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell cycle is governed by a family of cyclin-dependent kinases (Cdks). Cdk2 forms a functional complex with cyclin E and plays a pivotal role in the regulation of G1/S transition. Cdk2 activity is negatively regulated by interactions with inhibitors. p27Kip1, one of the most potent inhibitors of Cdk2, was recently identified as a powerful negative prognostic marker in non-small cell lung cancer as well as in colorectal and breast cancer. In the present study, the expression of p27 and Ki-67 antigen in nonneoplastic and cancerous lung tissues was determined by immunohistochemistry. After establishing that the antibody-measured p27 labeling index was a good reflection of the level of p27 expression measured by Western blotting, we show that p27 labeling index is decreased in cancerous lung tissues, compared with nonneoplastic lung tissues, and exhibits a significant inverse relation to the proliferation marker Ki-67 antigen, detected with monoclonal antibody MIB-1. Consistent with these data, all cancerous lung tissues showed enhanced degradation activity of p27 compared with nonneoplastic lung tissues and, in addition, increased levels of the phosphorylated form of Cdk2, as determined with Western blot analysis. The H1 histone kinase activity associated with Cdk2 was also increased in non-small cell lung cancers. Statistical analysis showed that proliferative activity as measured by MIB-1 labeling index was highly correlated with Cdk2 activity (r = 0.767, P < 0.0015). These results suggest that p27 and Cdk2 may play an important role in the proliferation of non-small cell cancer.
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PMID:Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer. 970 10

BACKGROUND: Prognostic factors for predicting the recurrence of node-negativebreast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. METHODS: This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors weresmaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of theprimary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. RESULTS: According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44v6, CD44v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (p &ly; 0.1; Wilcoxon-Mann-Whitney analysis). Chi-squared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p < 0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44v9 (p=0.02)were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p =0.01), and negativity for CD44v9 (p =0.03) were independent prognostic factors among the immunohistochemical markers examined. CONCLUSION: Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.
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PMID:Prognostic Factors for Node-negative Breast Cancers: Results of a Study Program by the Japanese Breast Cancer Society. 1109 54

Oligodendroglial tumors are mainly classified histologically into 2 types of tumors--oligodendrogliomas and oligoastrocytomas--whether the tumor includes astrocytic component or not, and these are, respectively, divided histologically into 2 different malignant groups, low-grade (WHO grade II) and high-grade or anaplastic (WHO grade III). In this study, we investigated the expression of the cell cycle-related proteins and analyzed the relationship between the labeling index (LI: the percentage of positive nuclei) of these proteins and 2 histopathological phenotypes, grade and prognosis. Forty-four specimens were examined, including 11 oligodendorogliomas (0), 5 oligoastrocytomas (OA), 18 anaplastic oligodendrogliomas (aO) and 10 anaplastic oligoastrocytomas (aOA), according to the WHO classification. Of these, 19 specimens were obtained from recurrent tumors of 8 cases. The mean LI of all the investigated proteins between O and OA, and aO and aOA showed no significant differences. The mean MIB-1 LI, pRb LI, p53 LI and p14 LI of GIII were significantly higher than GII, while the mean p27 LI of GIII was significantly lower than GII. In the recurrent cases, we noted correlations between the disease-free period and MIB-1 LI (inverse), p27 LI and p14 (inverse). Significant correlations were noted between MIB-1 LI and pRb LI, MIB-1 LI and cycD1 LI, MIB-1 LI and p27 LI (inverse), pRb LI and cycD1 LI, cycD1 LI and cdk4 LI and pRb LI and p27 LI (inverse) in the pRb/cycD1-cdk4/p27 pathway, and between MIB-1 LI and p53 LI, MIB-1 LI and p14 LI, p53 LI and p14 LI, p53 LI and MDM2 LI and MDM2 LI and p14 LI in the p53/MDM2/p14 pathway. In conclusion, both pRb/cycD1-cdk4/p27 and p53/N4DM2/p14 pathways correlate with malignant progression, and MIB-1 LI, pRb LI, p27 LI, p53 LI and p14 LI reflect the histopathological malignancy of oligodendroglial tumors. MIB-1 LI, pRb LI and p27 LI are especially useful as indicators of malignancy of oligodendroglial tumors.
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PMID:The expression of cell cycle regulatory proteins in oligodendroglial tumors. 1200 53

We describe the immunohistochemical profile of rare primary squamous carcinoma of the clitoris metastasizing to the bilateral inguinal lymph nodes. Several antigens were assessed immunohistochemically (pRb1, p16INK4A, cyclin D1, cdk4, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), p53, Ki-67, p27KIP1, PTEN, hMLh1, phospho-AKT, collagen IV, leptin and CD90) in both tumors. All the antibodies applied revealed a staining pattern that is typical of primary and metastatic carcinomas. Cyclin D1-cdk4 complex was overexpressed, whereas there was no p16INK4A immunostaining. Moreover, both tumors expressed positivity for p53 protein, but were negative for estrogen and progesterone receptors. The proliferative activity of cancer, assessed by MIB-1 Proliferative Index, amounted to 25% either for primary or for metastatic tumors. As a conclusion, immunohistochemical assessment of various cell-cycle-associated molecules yield clues as to their possible function during the process of spread of rare neoplasm originating from the clitoris.
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PMID:The immunohistochemical profile of the primary and metastatic carcinoma of the clitoris: a case report. 1616 59

We examined loss of heterozygosity (LOH) at the TP53 gene in primary human endometrial carcinomas (EC), and investigated the relationship between allelic loss, p53 protein overexpression, pRb-1 pathway alterations and MIB-1 proliferative activity. Applying the non-isotopic PCR-RFLP/VNTR-silver staining techniques, we investigated TP53 LOH in 46 tumors at four polymorphic loci. Out of 42 informative carcinomas, LOH was found in 19% of the cases studied. In general, there was no significant relationship between LOH and the clinical and pathological variables of cancer, including patient age, clinical stage, histological grade or depth of myometrial invasion. Interestingly, none of 7 tumors associated with hyperplasia revealed allelic imbalance, whereas 8 of 27 (30%) tumors without hyperplasia exhibited LOH (p=0.312; Fisher's exact test). Overexpression of nuclear p53 was not correlated with allelic loss at TP53 (p=0.336, Fisher's exact test). It is worth pointing out that p53 immunoreactivity was significantly related to proliferative activity of cancer (R=0.42, p=0.0037; Spearman's rank correlation test). A tendency towards a poorer outcome was reported in EC patients displaying TP53 LOH during short-time follow-up (p=0.093; log-rank test). None of the tumors simultaneously showed LOH at TP53 and RB1 genes (R=-0.211, p=0.16; Spearman's rank correlation test). p16INK4A alterations (LOH and gene deletion) occurred concomitantly, with 3 tumors showing the TP53 allelic loss, whereas the cyclin D1/cdk4 complex was overexpressed in a case with TP53 LOH. Altogether, losses at TP53 were not associated with p53 nuclear overexpression, but may affect a subset of EC patients characterized by an unfavorable prognosis at short-time follow-up. Allelic loss at TP53 seems to arise independently of LOH at the RB1 gene in carcinomas of the uterine corpus in humans. Disruptions at p16INK4A and/or cdk4/cyclin D1 concomitantly occurring with TP53 LOH may participate in the development of a subset of endometrioid-type ECs.
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PMID:Allelic loss at TP53 is not related to p53 protein overexpression in primary human endometrial carcinomas. 1629 76