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

We studied the immunolocalization of cyclins D1 and E and their corresponding partner cyclin dependent kinases (cdk), cdk4 and cdk2 in 41 cases of human breast malignancy (21 invasive ductal carcinomas and 19 invasive lobular carcinomas) and examined the correlation of the labeling indexes among these cyclins, cdks, Ki67, estrogen receptor (ER) and progesterone receptor (PR). Cyclin D1 immunoreactivity was observed exclusively in the nuclei of tumor cells in 27/41 (65%) of the cases examined. Immunoreactivity for cyclin E and cdk2 was detected in all the cases and observed in the nuclei of both carcinoma and non-carcinoma cells. cdk4 immunoreactivity was detected in 39/41 (95%) cases and found in carcinoma and non-carcinoma cells. In all carcinomas examined, a significant correlation was observed only between Ki67 and cyclin D1 (p = 0.0037). However, when examining only invasive ductal carcinomas, a significant correlation was detected between Ki67 and cyclin D1 (p = 0.0069), Ki67 and cdk2 (p = 0.0043) and cyclin D1 and cdk4 (P = 0.0024). Only cyclin D1 correlated with the pathologic stages of the disease and histological grades of invasive ductal carcinoma. Among these cyclins and cdk, overexpression of cyclin D1 is considered to play an important role in the development of human breast malignancy through abnormal proliferation. No significant correlation was observed between steroid receptor status and any of cyclins and cdks examined. Cyclin D1 and cdk2 expression correlated with cell proliferation (Ki67) and cyclin D1 expression with expression of cdk4 in invasive ductal carcinoma but not invasive lobular carcinoma. Cyclin E expression did not correlate with cell proliferation, cyclin D1 or cdks possibly due to deregulation of its expression. These results also indicate different patterns of cyclin D1, cyclin E, cdk2 and cdk4 expression between invasive ductal and lobular carcinoma of human breast.
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PMID:Immunolocalization of cyclins D and E and cyclin dependent kinase (cdk) 2 and 4 in human breast carcinoma. 941 24

: Phosphatidylinositol 3'-kinase (PI3K) and Akt mediate survival signals and allow the cells to escape apoptosis in various human cancers. We postulated that LY294002, a PI3K inhibitor, might inactivate Akt, consequently inhibiting cell proliferation in 3 human pancreatic ductal carcinoma cell lines, PSN-1, PANC-1, and KP-4. LY294002 (50 micromol/L) caused a decrease in phosphorylated Akt and inhibition of cell proliferation in a time-dependent manner, but there was no obvious induction of apoptosis. Flow cytometric analysis revealed that pancreatic cancer cells treated with 50 micromol/L LY294002 underwent G1 arrest, which was associated with dephosphorylation of the ppRB protein, a decrease in the protein expression of cyclin D and E, and their activating partners Cdk2, 4, and 6 with simultaneous accumulation of P27/Kip1. Our data indicate that P27/Kip1 accumulation by Akt inactivation could induce cell cycle arrest in the G1 phase and suggest that the PI3K-Akt pathway plays an important role in cell proliferation in human pancreatic ductal carcinoma cells.
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PMID:Role of the phosphatidylinositol 3'-kinase-Akt signal pathway in the proliferation of human pancreatic ductal carcinoma cell lines. 1508 85

A common feature of human breast oncogenesis is cell cycle deregulation. The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August Copenhagen Irish (ACI) rats. Low serum E(2) levels ( approximately 60-120 pg/ml) were sufficient to induce mammary gland tumors (MGTs) that remarkably resemble human ductal breast cancer (BC) at the histopathologic and molecular levels. Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) expression compared with age-matched untreated controls. Small focal dysplasias with large, pale staining nuclei were commonly seen at 3-3.6 months, large focal dysplasias, including atypical ductal hyperplasia at 3.6-4.3 months, ductal carcinoma in-situ (DCISs) at 4.3-5.0 months, and 100% incidence of invasive ductal BC/frank tumors at 5-6 months were detected after E(2) treatment. Immunohistochemical analysis of serial sections of focal dysplasias, DCISs and invasive ductal carcinomas showed overexpression of cyclins D1, D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined essentially to early pre-malignant lesions (focal dysplasias and DCISs) and primary MGTs with <1-5% of resting and normal hyperplastic breast cells staining positive. The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to cdk4 was significantly elevated. Semi-quantitative reverse transcriptase PCR analysis of the E(2)-induced MGTs exhibited increased expression of cyclins D1 (2.9-fold) and D3 (1.4-fold) mRNA, indicating that their elevated protein expression was due in part to an increase in mRNA transcription. However, when analyzed by quantitative real-time Q-PCR, these genes were not amplified. These data indicate that in female ACI rat mammary glands, E(2)-induced pre-malignant lesions differentially and selectively express cyclins D1 and D3, thus contributing to a distinct growth advantage of these pre-neoplasias relative to E(2)-elicited normal hyperplasia.
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PMID:Overexpression of cyclins D1 and D3 during estrogen-induced breast oncogenesis in female ACI rats. 1631 Dec 45