Cathepsin D in breast cancer

Rochefort, Henri

doi:10.1007/bf01806570

Cited by 92 publications

(46 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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). There have been changes in (1) the proportion of patients available for study from the whole population attending our Breast Clinic (12%, 15% and 33% respectively in the references Miller et al., 1990;Miller et al, 1993 and the present work); (2) the proportion of patients studied who had high levels (>8000 fmol mg-' protein) of cyclic AMP-binding in their tumours (12%, 9% and 3% respectively); and (3) the proportion of patients studied who received adjuvant or primary endocrine therapy (40%, 67% and 80% respectively). Thus, the most likely explanations for the differences between the present and earlier studies are that: (1) propose to update our study after further follow-up.…”

Section: Resultsmentioning

confidence: 99%

“…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) studies.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Prospective evaluation of prognostic factors in operable breast cancer

Hawkins

Tesdale²,

Killen³

et al. 1996

Br J Cancer

View full text Add to dashboard Cite

(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)

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Prospective evaluation of prognostic factors in operable breast cancer

Hawkins

Tesdale²,

Killen³

et al. 1996

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Furthermore, a recent study showed that vascular invasion was observed in 47% of tumours excised between days 3 and 12 of the cycle but in only 33% of those undergoing surgery at other times (Badwe et al, 1995). In vitro, oestrogens modulate secretion of at least two proteases, plasminogen activator (Mira-yLopez et al, 1991) and cathepsin D (Rochefort et al, 1990) which can activate a cascade of proteolysis (He et al, 1989). The ability to secrete these proteases has been shown to be an independent adverse predictor of survival in breast cancer (Rochefort, 1990;Duffy et al, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, oestrogens modulate secretion of at least two proteases, plasminogen activator (Mira-yLopez et al, 1991) and cathepsin D (Rochefort et al, 1990) which can activate a cascade of proteolysis (He et al, 1989). The ability to secrete these proteases has been shown to be an independent adverse predictor of survival in breast cancer (Rochefort, 1990;Duffy et al, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

Body weight and vascular invasion in post-menopausal women with breast cancer

Fentiman¹,

Millis²,

Gregory³

1997

Br J Cancer

View full text Add to dashboard Cite

Summary To examine the relationship between body weight and vascular invasion (VI) around tumours in post-menopausal women with operable breast cancer, a retrospective study was conducted of 393 patients treated in a breast unit between 1987 and 1991. Weight was measured at the time of diagnosis. Vascular invasion was recorded as being present or absent. Vascular invasion was seen in slightly more of the 50 perimenopausal patients than in the 343 post-menopausal women (44% vs 36%). In the tumour specimens from post-menopausal patients weighing <50 kg, VI was observed in 11% compared with 45% of those weighing more than 80 kg (P = 0.02). Furthermore, the 5-year survival of those with VI was 74% compared with 91% for those without (P < 0.0001). Menopausal status and body weight may influence survival in patients with breast cancer, possibly as a result of the presence of unopposed circulating oestrogens at the time of surgery. Oestrogens may alter cohesiveness of breast cancer cells and modulate secretion of proteases, thereby influencing invasive potential.Excision of tumours in such an environment may have a deleterious impact on survival.Keywords: breast cancer; prognosis; weight; post-menopausal women; vascular invasionThe prognosis of women with operable breast cancer depends upon tumour type, axillary nodal involvement and also menopausal status (Adami et al, 1986;Caleffi et al, 1989). Premenopausal cases have the lowest hazard rates for relapse and death. Rates are intermediate in post-menopausal women and the highest rates are found in perimenopausal women, that is those within 5 years of last menstrual period (Langlands et al, 1989). The observed differences may be due to the different hormonal environment to which tumours are exposed in these three groups of women.Survival has been shown to be inversely related to body weight in the majority of studies (Boyd et al, 1981; Tartter et al, 1981;Newman et al, 1986;Tretli et al, 1990; Senie et al, 199 la;Vatten et al, 1991), but such a relationship is less obvious in premenopausal women (Greenberg et al, 1985). Although there is a relation between body weight and other prognostic factors, such as tumour size and axillary lymph node involvement, the effect of obesity remains an independent factor in multivariate analysis (Tarttar et al, 1981;Vatten et al, 1991). The mechanism through which menopausal status and body weight influence survival is uncertain, although it is known that most circulating oestrogens in postmenopausal women are derived from peripheral aromatization of adrenal androgens in subcutaneous fat. Thus, more obese women have higher plasma levels of oestrogens (Grodin et al, 1973).Additionally, the impact of obesity on survival is more pronounced among those women with oestrogen receptor-positive breast cancers (Verreault et al, 1989).The risk of relapse and death also depends upon the metastatic potential of the tumour as manifested by the presence of malignant Correspondence to: IS Fentiman cells in lymphatic channels and blood vessels (vascu...

show abstract

“…In hormone-independent breast cancer cell lines such as MDA MB-231 (that do not express ERa), pS2 is not expressed and cathepsin D is constitutively expressed. In the primary tumor of breast cancer patients these two markers have opposite signi®cance, cathepsin D being associated with a poor prognosis (Rochefort, 1990), whereas pS2 is associated with a good prognosis (Foekens et al, 1993). One explanation for this di erence is that cathepsin D, but not pS2, is over-expressed in ER negative breast cancers.…”

Section: Introductionmentioning

confidence: 99%

Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines

et al. 1999

Self Cite

View full text Add to dashboard Cite

We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identi®cation of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormonedependent MCF7 cell line, within the pS2 gene 5'-anking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located 710.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor a, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor a, there was only one hormoneindependent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-¯anking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions 72.3 Kb and 73.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormoneindependent DNase I hypersensitive site, catD-HS4, located at position 74.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.

show abstract

Cathepsin D in breast cancer

Cited by 92 publications

References 34 publications

Prospective evaluation of prognostic factors in operable breast cancer

Prospective evaluation of prognostic factors in operable breast cancer

Body weight and vascular invasion in post-menopausal women with breast cancer

Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines

Contact Info

Product

Resources

About