Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the various factors reported as having significant prognostic value in primary breast cancers, the author discusses the value of well established "classical" prognostic factors used routinely and "new" prognostic factors developed over recent years as a result of progress in cell and molecular biology. The presence of axillary lymph node metastases remains the most important prognostic factor of recurrence, justifying post-surgical adjuvant therapy. However, in patients with negative axillary nodes (N-), the size of the tumour, Scarff-Bloom-Richardson (SBR and MSBR) histological grade, certain particular histological types (carcinoma in situ and tubular, colloid or pure papillary cancer) and hormone receptors (ER and PR) appear to be well established prognostic factors allowing the identification, within this group of N- patients who generally have a good prognosis, those patients with a low risk of recurrence and therefore not requiring adjuvant therapy. In contrast, the proliferative activity (ploidy and S phase, Thymidine Labeling Index, antibody Ki67), cathepsin D, thymidine kinase, EGF receptors, several genes including oncogene HER-2/neu, are recently developed prognostic factors whose significance needs to be confirmed by further studies.
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PMID:[Prognostic factors in breast cancer]. 134 Jan 64

The MDA-468 human breast cancer cell line displays the unusual phenomenon of growth inhibition in response to pharmacological concentrations of EGF. This study was initiated with the objective of elucidating the cellular mechanisms involved in EGF-induced growth inhibition. Following EGF treatment the percentage of MDA-468 cells in G1 phase increased, together with a concomitant depletion in S and G2/M phase populations, as revealed by flow cytometry of DNA content. The apparent G1 block in the cell cycle was confirmed by treating the cells with vinblastine. DNA synthesis was reduced to about 35% of that measured in control, untreated cells after 48 h of EGF treatment, as measured by the incorporation of [3H]thymidine. DNA synthesis returned to normal following the removal of EGF from the growth-arrested cells. In order to locate the EGF-induced event responsible for the G1 arrest more precisely, we examined the expression of certain cell cycle-dependent genes by Northern blot analysis. EGF treatment did not alter either the induction of the early G1 marker, c-myc, or the expression of the late G1 markers, proliferating cell nuclear antigen, and thymidine kinase. However, EGF-treated cells revealed down regulation of p53 and histone 3.2 expression, which are expressed at the G1/S boundary and in S phase, respectively. These results indicate that EGF-induced growth inhibition in MDA-468 human breast cancer cells is characterized by a reversible cell cycle block at the G1/S boundary.
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PMID:EGF-dependent growth inhibition in MDA-468 human breast cancer cells is characterized by late G1 arrest and altered gene expression. 167 99

Somatic cell hybrids were obtained with electric pulse by fusion of human epithelial HeLa cells derived from a carcinoma of the uterine cervix and mouse fibroblasts 3T3.4E, deficient in thymidine kinase. Hybrids were selected and propagated in HAT media; some experiments were carried out in medium with delipidized serum. The hybrid cells were characterized by indirect immunofluorescence with a biotin-streptavidin system using a panel of nine monoclonal antibodies specific for membrane and cytoplasmic antigens of parental cells: intermediate filaments (keratins and vimentin), HLA class 1 (beta 2-microglobulin), cell activation (EGF and transferrin receptors) and cellular adhesion (fibronectin and laminin). All of these antigens were expressed in HeLa cells cultured in conventional medium or with delipidized serum. Conversely mouse fibroblasts contained only vimentin, fibronectin and laminin. All the parental antigens were present in first passage hybrid cells cultured in conventional medium. Vimentin, fibronectin and laminin were maintained in fourth passage hybrids whereas keratins, beta 2-microglobulin, EGF and transferrin receptors were no longer detected. When propagated in medium with delipidized serum, hybrid cells re-expressed these antigens after 5 days of culture. These findings suggest that the reexpression of HeLa cell antigens in hybrid cells was related to deficiency in vitamin A.
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PMID:Antigenic immunostaining patterns in somatic hybrids of human HeLa cells and mouse fibroblasts 3T3.4E propagated in conventional medium and delipidized serum. 248

In our view, two major areas of the investigation of the aging process have been most fruitful over the past few years: namely, the genetic and hormonal strategies aimed at the understanding of in vitro cellular senescence. The genetic studies have primarily utilized cell fusion techniques and viral probes. Along with cell cycle studies involving the induction of thymidine kinase activity and TTP synthesis, the cell fusion studies are most consistent with a late G1 block in senescent cells. This effect would appear to be distinct from the G0 arrest of density-inhibited or mitogen-restricted cell populations. The hormonal studies which have centered on the regulation of cell proliferation have recently focused on peptide hormones. EGF has been of particular interest since it is so well characterized. This receptor system remains largely unchanged throughout the lifespan with the notable exception of the purified receptor-associated, autocatalytic, tyrosine-specific kinase activity, which decreases with age. The functional significance of this decrease in enzyme activity is unknown, although its growth regulatory importance is implicated in several systems, and may well represent a critical early G0/G1 event which is absent in senescent cells.
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PMID:Cellular senescence: factors modulating cell proliferation in vitro. 299 27

125I-EGF binding technique was used to demonstrate high affinity receptor binding for epidermal growth factor (EGF-R) in 72 human mammary carcinomas. 27% of the tumors were EGF-R positive and the presence of this receptor was correlated with receptor levels for estradiol, DNA-pattern, proliferative index, thymidine kinase, tumor size, number of lymph node metastases and 6-year relapse probability. Our results confirm previous reports of an inverse relation between the cellular content of EGF-R and ER. In addition, we could associate EGF-R positivity with an aneuploid DNA-pattern and an increased growth rate, as measured by proliferative index. No correlation was found between EGF-R positivity in the primary tumor and presence of axillary lymph node metastasis at the time of operation. The 6-year relapse rate was somewhat higher for patients whose primary tumors were EGF-R positive. Moreover patients who had lymph node metastases at the time of operation and EGF-R positive tumors experienced a significantly lower 6-year disease free survival rate as compared to those who were node negative and had receptor negative tumors. It remains to be shown whether EGF-R alone can be used as an independent prognostic factor.
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PMID:Prognostic significance of the receptor for epidermal growth factor in human mammary carcinomas. 363 6

We have previously isolated 3T3 cell variants unable to respond to specific mitogens. In this report we analyze the dominant and/or recessive nature of these variants. Two independently isolated EGF nonproliferative variants are unable to bind EGF. Hybrids between 3T3R5 cells (thymidine kinase deficient, ouabain-resistant) and these variants express EGF receptors; the "EGF receptorless" phenotype of these variants is recessive. Hybrids between these two variants do not bind EGF; they are defective in a common, non-complementing function. A TPA nonproliferative 3T3 variant is also recessive; hybrids with 3T3R5 mount a mitogenic response to TPA. In contrast a fourth variant, which can neither bind labeled EGF nor respond to TPA, is dominant for both characteristics. Hybrids between this latter variant and 3T3R5 can neither bind EGF nor mount a mitogenic response to TPA.
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PMID:Dominant and recessive mitogen-nonproliferative variants of 3T3 cells. 387 70

The composition and response of the retinoid signaling pathway in a human cell line (CC-1), representative of a low grade cervical carcinoma, were evaluated. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated expression of cytoplasmic retinol binding protein, CRBPI, cytoplasmic retinoic acid binding protein, CRABPII, and nuclear retinoic acid receptors, RAR alpha, RARgamma, RXR alpha, and RXRbeta, but not CRABPI or RARbeta. This pattern is similar to that of the ectocervix. Activation of endogenous nuclear receptors was evaluated in a reporter subline of CC-1, called CC-B, containing a reporter gene controlled by a retinoic acid responsive element (RARE) and thymidine kinase promoter. Retinoid treatment of CC-B resulted in dose-dependent increases in reporter gene expression. Retinoids inhibited growth at concentrations greater than 100 nM. 9-cis retinoic acid (1 nM) significantly stimulated growth. Immunohistochemical analysis of CC-B organotypic cultures demonstrated a high level of epidermal growth factor receptor (EGF-R) expression that was decreased by retinoids. The degree of RARE transactivation induced by retinoids significantly correlated with the degree of inhibition of growth (R = -0.96) and EGF-R expression (R = -0.92). The dose-dependent and retinoid-specific responses of CC-1 at the molecular and biological levels demonstrate the utility of this reporter cell line for evaluation of retinoid activities.
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PMID:Biological assay for activity and molecular mechanism of retinoids in cervical tumor cells. 923 31