Cyclic AMP binding proteins and prognosis in breast cancer

Miller, William R.; Elton, R. A.; Dixon, JM; Chetty, U.; Watson, David

doi:10.1038/bjc.1990.48

Cited by 30 publications

(20 citation statements)

References 8 publications

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“…that these, too, being found in both tumour cells and macrophages (Yamamoto et al, 1987), may reflect the degree of inflammation in the tumour, rendering high levels of these proteins a sign of poor prognosis. In a previous, retrospective study (Miller et al, 1990), we have found that patients with high levels of cyclic AMP binding had a very short disease-free survival, this finding being confirmed in a second, prospective study (Miller et al, 1993). Careful comparison of these previous studies with the present work shows some changes over the years during which the studies were conducted: 1979conducted: -84 (Miller et al, 19901984-87 (Miller et al, 1993);and 1990-91 (present work).…”

Section: Resultssupporting

confidence: 70%

“…The proteolytic enzyme, cathepsin D (Mr 52 kDa), has been suggested to be involved in metastasis formation and reported in several studies also to be a sign of bad prognosis when present in high levels (for a review see Rochefort, 1990). Lastly, work in our own laboratories and elsewhere has demonstrated that high levels of cyclic AMP-binding protein(s), the regulatory subunits of the enzyme protein kinase A, represent another sign of poor prognosis, in both retrospective (Miller et al, 1990) and prospective (Miller et al, 1993) studies.…”

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confidence: 99%

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Prospective evaluation of prognostic factors in operable breast cancer

Hawkins

Tesdale²,

Killen³

et al. 1996

Br J Cancer

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(Osborne, 1992) and different studies of prognosis have yielded widely differing results (Hawkins, 1993). We have selected four putative biochemical indices of prognosis and evaluated them in a prospective study. The putative markers chosen were the oestrogen receptor (ER), the epidermal growth factor receptor (EGFR), cathepsin D (cath D) and cyclic AMP-binding protein(s) (c-AMP-b).The oestrogen receptor, a nuclear protein (Mr 66 kDa) has been shown to relate to both endocrine sensitivity (Jensen, 1975) and prognosis in multiple studies, including our own previous work (Humeniuk et al., 1982;Hawkins et al., 1987aHawkins et al., , 1991, although some consider that it is only of prognostic significance in the early years after treatment (e.g. Saez et al., 1983). The receptor for epidermal growth factor is a membrane protein (Mr 180 kDa), which has been reported to be a sign of bad prognosis, again in multiple studies (Sainsbury et al., 1987;Gasparini et al., 1992). The proteolytic enzyme, cathepsin D (Mr 52 kDa), has been suggested to be involved in metastasis formation and reported in several studies also to be a sign of bad prognosis when present in high levels (for a review see Rochefort, 1990). Lastly, work in our own laboratories and elsewhere has demonstrated that high levels of cyclic AMP-binding protein(s), the regulatory subunits of the enzyme protein kinase A, represent another sign of poor prognosis, in both retrospective (Miller et al., 1990) and prospective (Miller et al., 1993)

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Section: Resultssupporting

confidence: 70%

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confidence: 99%

Prospective evaluation of prognostic factors in operable breast cancer

Hawkins

Tesdale²,

Killen³

et al. 1996

Br J Cancer

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“…Furthermore, cAMP and cAMP-dependent protein kinase levels have been reported to be lower in human colorectal cancers and villous adenomas than in normal mucosa (Alexandrov et al, 1986). By contrast, in breast cancer cAMP-BP levels are of independent prognostic significance (Miller et al, 1990) with higher levels of binding being associated with reduced disease free interval and decreased survival. The aim of this study was to determine the levels of cAMP-BP in human colorectal cancers and related mucosa and to correlate these levels to known prognostic factors; namely stage and grade.…”

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confidence: 94%

Cyclic adenosine 3',5'-monophosphate binding proteins in human colorectal cancer and mucosa

Bradbury

Miller²,

Dc³

1991

Br J Cancer

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Summary Cyclic AMP Binding Proteins (cAMP-BP) levels have been measured by means of a competitive binding assay in the cytosols of 50 human colorectal cancers. These levels have been related to those in mucosa both adjacent to and distant from the tumour in the same patients. Cyclic AMP-BP were higher in tumour than in either adjacent (P<0.000001) or distant mucosa (P<0.00001). Binding of cAMP in adjacent mucosa was lower than that in distant mucosa (P<0.0001). There was no significant difference in the level of binding between tumours arising from different sites in the colon and binding was not related to age or sex of the patient. However, binding was higher in Dukes' B than Dukes' C cancers (P<0.005). There was also a trend for cAMP binding levels to be higher in moderately differentiated than in poorly differentiated cancers (P = 0.07). Thus cAMP-BP appear to be over-expressed in human colorectal cancers and levels are related to the stage and grade.Cyclic adenosine 3',5'-monophosphate (cAMP) functions as a secondary messenger for a wide range of hormones releasing factors and drugs. The cAMP signalling system also interacts with other signalling pathways that are used by locally-acting growth factors (Olashaw & Pledger, 1988) to bring about co-ordinated control of basic cell processes such as proliferation and differentiation. Cyclic AMP exerts all its known effects through binding to and activating a specific cAMPdependent protein kinase, also known as Protein Kinase A (PK-A) (Taylor et al., 1989). PK-A is a tetrameric holoenzyme comprising two regulatory units (R), and two catalytic units (C). R units, also known as cAMP binding proteins (cAMP-BP) act as pseudosubstrate for the C units and so prevent them from carrying out phosphorylation within the cell (Shenolikar, 1988). Activation of PK-A follows binding of cAMP to R units and their dissociation from the C unit. As well as leading to protein phosphorylation, activation PK-A also brings about changes in expression of cAMP dependent genes, although the exact mechanisms are, as yet, unclear (Roesler et al., 1988). Conventionally, cAMP has been considered a negative signal to cellular proliferation although stimulatory effects have been described depending on the cell type, phase in the cell cycle and presence of other growth factors (Dumont et al., 1989). Cyclic AMP analogues have been shown to inhibit the growth and promote the differentiation of a number of human cancer cell lines in vitro including those derived from colorectal cancer (Ally et al., 1988). In animal studies the production of colonic tumours by chemical carcinogens has been associated with decreased levels of PK-A activity (DeRubertis & Craven, 1980). Furthermore, cAMP and cAMP-dependent protein kinase levels have been reported to be lower in human colorectal cancers and villous adenomas than in normal mucosa (Alexandrov et al., 1986). By contrast, in breast cancer cAMP-BP levels are of independent prognostic significance (Miller et al., 1990) with higher levels of binding being associ...

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“…The study was prompted by work previously carried out on human breast cancers (Miller et al, 1990) indicating a link between levels of cAMP-binding proteins and eventual outcome of the disease. The results showed that high cAMP-binding protein levels are an indicator of poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, levels of cAMP-binding proteins in rodent mammary carcinomas Bodwin et al, 1980;Cho-Chung et al, 1981) vary according to the degree of autonomy and growth status of the tumour. More recently, it has been reported that high levels of tumour cAMP-binding proteins are associated with poor prognosis in patients with breast cancer (Miller et al, 1990 (0,0.005,0.05,5,50,50011M). With respect to all other parameters, the binding assays were carried out as described previously.…”

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confidence: 99%