Increased activities of thymidine kinase isozymes in human mammary tumours

Sakamoto, Shinobu; Iwama, Takeo; Ebuchi, Masakazu; Tsukada, Kunio; Sagara, T; Kawasaki, Tohru; Murakami, Saburo; Kasahara, Noriyuki; Kudo, Hideki; Okamoto, Reiko

doi:10.1002/bjs.1800730409

Cited by 22 publications

(8 citation statements)

References 5 publications

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“…The median value for TS in tumour tissue was approximately tenfold higher than that of the normal large bowel crypt TS levels measured in those samples with adjacent normal mucosa. Again, these results are similar to those reported earlier in the literature on TS catalytic activity (Sakamoto et al, 1993;Etienne et al, 1995).…”

Section: Discussionsupporting

confidence: 92%

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy

Findlay

Cunningham²,

Morgan³

et al. 1997

Br J Cancer

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Section: Discussionsupporting

confidence: 92%

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy

Findlay

Cunningham²,

Morgan³

et al. 1997

Br J Cancer

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“…This is supported by the finding that rapidly proliferating tumour cells in culture release TK into the surrounding medium (Bristow et al, 1988). The results described in the present communication would also correspond with the tumour cells being the source of the elevated serum TK levels since Sakamoto et al (1986) has reported that both isozyme forms of TK are elevated in human mammary tumours with TKI showing the greater increase in activity.…”

Section: Resultssupporting

confidence: 87%

Thymidine kinase activities in mononuclear leukocytes and serum from breast cancer patients

McKenna

O’Neill²,

Abram³

et al. 1988

Br J Cancer

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Summary Levels of the nucleotide pathway enzyme thymidine kinase (TK) were assayed in the mononuclear leukocytes and serum of 70 female patients with breast cancer and 98 male and 77 female non-cancer hospital patients. The total TK levels in both mononuclear leukocytes and serum from patients with breast cancer were significantly higher than in controls. The serum TK levels showed a significant correlation with cancer stage. No such correlation was observed with mononuclear leukocyte TK levels. Serum TK from 20 patients with breast cancer and 19 control patients was further assayed to ascertain the relative contributions of the thymidine kinase isozymes TK1 and TK2 to total TK levels. The increase in serum TK from breast cancer patients appears to be due to an increase in both TKl and TK2 levels.The pyrimidine nucleotide salvage pathway enzyme, thymidine kinase (TK), occurs mainly in two forms in human tissue (for review, see Kit, 1976). TKl is the cytosolar TK and has high activity in dividing cells but is absent in resting cells (Bello, 1974). This form of the enzyme has therefore high activity in foetal and neoplastic tissue, but low activity in non-growing adult tissue (Gordon et al., 1968;Machovich & Greengard, 1972;Caron & Unsworth, 1978 Total TK (i.e., TKl + TK2) levels have been found to be elevated in the serum of rats bearing transplanted hepatomas (Taylor et al., 1981). Kreis et al., (1982) found a substantial increase in total TK levels in the plasma of mice with advanced leukaemias and in humans with acute non-lymphocytic leukaemia, chronic myelocytic leukaemia, pancreatic cancer (with metastasis to liver), fibrohistiocytoma, carcinoid syndrome (with metastasis to bone), and prostate cancer (with metastasis to bone). More recently it has been found that there are elevations in serum total TK levels in patients with non-Hodgkin's lymphoma and cancers of bone (metastatic, primary site unknown), squamous cell, prostate, brain and basal cell (O'Neill et al., 1986(O'Neill et al., ,1987. The increases in serum total TK activities appear to be largely the result of increased TKI levels (O'Neill et al., 1987). This is in agreement with the observations of other workers who have found elevated serum TKI levels in patients with adult nonHodgkin's lymphoma (Ellims et al., 1981b;Gronowitz et al., 1983), acute lymphoblastic and non-lymphoblastic leukaemia as well as chronic myelogenous leukaemia (Hagberg et al., 1984), childhood acute lymphoblastic leukaemia (Morgan et al., 1985), Hodgkin's lymphoma (Eriksson et al., 1985), multiple myeloma (Simonsson et al., 1985) and secondary brain tumours (McKenna et al., 1985). Thymidine kinase assays were based on methods previously described (O'Neill et al., 1986;McKenna et al., 1985). After separation the mononuclear leukocytes were washed twice in Hank's BSS, were resuspended in 0.5ml of extraction buffer containing 0.02M Tris (pH7.8) paper discs. The discs were subsequently washed three times (3 x 5min) in 0.00 1M ammonium formate (1Oml/disc), washed in distill...

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“…Since rapid replication of DNA requires an adequate supply of deoxyribonucleotides to serve as the substrates for the DNA polymerase reaction, it is not surprising that the activity of this enzyme has been shown to be regulated in response to alterations in DNA replicative activity. High TK activity has been consistently observed in rapidly proliferating normal, fetal and neoplastic tissues Sakamoto et al 1984Sakamoto et al , 1985Sakamoto et al , 1986Sakamoto et al , 1987Luccioni et al 1988). Two distinct isozymes of TK have been separated and purified by various methods, including polyacrylamide gel electrophoresis (PAGE), subcellular fraction, affinity column chromatography, and DEAE-cellulose column chromatography (Kit 1978).…”

Section: Discussionmentioning

confidence: 99%