Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study (original) (raw)
Related papers
Relation of cathepsin D level to the estrogen receptor in human breast cancer
International journal of clinical & laboratory research, 1992
Seventy-three primary human breast cancers were analyzed to assess the presence of estrogen and progesterone receptors, the p29 protein, and the total cathepsin D status. No significant relationship was found between cathepsin D concentration and the presence of ER or PR, either by Fisher's exact test or Spearman's rank correlation (P greater than 0.1). However, a significant association was found between cathepsin D and p29 (Fisher's exact test, P less than 0.001) and between cathepsin D and steroid receptor status in samples expressing both estrogen and progesterone receptors (positive by steroid binding assay and enzyme immunoassay) (P less than 0.05). This association was more significant in tissues expressing estrogen and progesterone receptors as well as p29 (P less than 0.001). In contrast, cathepsin D synthesis was not related to tumor size, lymph node involvement, or patient's age (P greater than 0.05). Steroid receptors and cathepsin D were also assayed in ...
Archive of oncology, 2002
Background: Cellular biomarkers may predict tumor cell behavior in breast cancer. One of the most paradoxical biomarker in breast cancer is cathepsin D. Patients and methods: The study includes 152 patients with histologically verified breast carcinoma. Clinicopathological findings were classified according to classical breast carcinoma-host features (age and menopausal status) and carcinoma features (lymph node status, tumor size type and grade). Estrogen and progesterone receptors were assayed in accordance with the recommendation of the EORTC. Cathepsin D concentrations were determined using immunoradiometric assay. The results were analyzed using non-parametric statistical methods. Results: All differences in the proportion of breast carcinoma classified as cathepsin D-positive and disagreements on the association of cathepsin D status with clinicopathological features of breast cancer are the result of varying cut-off values used by different authors. Using the cut-off value, w...
Nucleic Acids Research, 1988
The estrogen-induced 52K protein secreted by human breast cancer cells is a lysosomal protease recently identified as a pro-cathepsin D by sequencing several cDNA clones isolated from MCF_ cells (Augereau et al., Mol. Endocr.). Using one of these clones, we detected, in MCF 7 cells, a 2.2 kb mRNA whose level was rapidly increased 4-to 10-fold by estradiol, but not by other classes of steroids. Other mitogens, such as epidermal growth factor and insulin, also induced the 2.2 kb mRNA in a dose-dependent manner. Induction with epidermal growth factor was as rapid but was 2-to 3-fold lower than with estradiol. Antiestrogens had no effect on the 52K-cathepsin-D mRNA in MCF ? cells, but became estrogen agonists in two antiestrogenresistant sublines R, 7 and LY2. The use of transcription and translation inhibitors and nuclear run-on experiments indicate that estradiol enhances transcription of the 52K-cathepsin-D gene in MCF™ cells. URL Press Limited, Oxford, England. 1903 by guest on September 15, 2016 http://nar.oxfordjournals.org/ Downloaded from
Relationship between Cathepsin-D and Other Prognostic Factors in Human Breast Cancer
Tumori Journal, 1997
Cathepsin-D (CATH-D) is a lysosomal protease induced by estrogens in estrogen receptor-positive breast cancer cell lines and constitutively produced by estrogen receptor-negative breast cancer cells. The concentration of CATH-D in the cytosol of 97 human breast tumor tissues was correlated with other well-known prognostic factors for human breast cancer. CATH-D was significantly higher in node-positive than in node-negative tumors (P = 0.042, Kruskal-Wallis test). However , no correlation was found between enzyme levels and the number of positive nodes. CATH-D concentration did not correlate with age, menopausal status, clinical stage of the disease, size of the primary tumor, steroid receptors, thymidine labeling index, histological grade, nuclear grade or cellularity. CATH-D did not show any association with the known prognostic factors evaluated in this study and its association with lymph nodes was only weak.
Clinical chemistry, 1991
Cathepsin D (CD, EC 3.4.23.5) is a lysosomal protease induced by estrogen in certain estrogen receptor (ER)-positive breast cancer cell lines but produced constitutively by ER-negative cell lines. Our aims in this investigation were to study the distribution of CD in human breast cancers and to relate its concentrations to various biochemical, histological, and clinical characteristics. The concentrations of CD were significantly higher in breast carcinomas than in either normal breast tissues or benign breast tumors. In primary carcinomas, CD concentrations did not correlate with the concentrations of ER or with the estrogen-inducible protease t-PA. However, CD concentrations did correlate weakly but significantly with both UK-PA antigen and UK-PA activity. Also, CD concentrations did not correlate with either tumor stage or axillary node status but did correlate significantly with tumor grade. Patients with cancers containing high concentrations of CD had a significantly shorter o...
Biological and Clinical Significance of Cathepsin D in Breast Cancer
Acta Oncologica, 1992
an aspartyl protease of lysosomes, is overproduced and hypersecreted by breast cancer cells. The prognostic value of its immunoassay in breast cancer cytosol is reviewed from the first retrospective clinical studies available, which show a strong correlation between high concentrations of cathepsin D in the cytosol of primary tumor and further occurrence of metastasis. This new prognostic factor is induced by estrogen in hormone dependent breast cancer but expressed at a high level in hormone independent breast cancer and appears to be independent of other more classical factors. Its value in node negative patients varies according to the studies. In nude mice, transfection of cathepsin D cDNA into tumor cells increases their metastatic potential, suggesting that overexpression of this protease may be one of the factors responsible for metastasis in human breast cancer. The mechanism by which this protease might facilitate metastasis in vivo is still unknown, even though cathepsin D has the potential to initiate a proteolytic cascade, to degrade extracellular matrix and to liberate FGFs like growth factors from the matrix. These studies should stimulate the search for new therapeutical agents in order to inhibit cathepsin D action.
Biochimie, 1988
m In estrogen-receptor-positive human breast cancer cell lines (MCF'/, ZR75-1), estrogens specifically increase the secretion into the culture medium of a 52,000 Da (52K) glycoprotein and stimulate cell proliferation. The 52K protein has been purified to homogeneity using monoclonal antibodies and identified as the secreted precursor of a cathepsin D bearing mannose-6-phosphate signals. The secreted precursor 52K protein is mitogenic in vitro in estrogen-deprived MCF7 cells, can be taken up by these cells via mannose-6-phosphate receptors, and can degrade extraceilular matrix and proteoglycans following its auto-activation. The protease is also produced constitutively by ER-negative cell lines, and is inducible by tamoxifen in some antiestrogen-resistant variants. The corresponding eDNA has been cloned using N-terminal sequencing of the protein and monoclonal antibodies. Its complete sequencing indicates a strong homology with pro-cathepsin D of normal tissues. Using a cDNA probe, the regulation of 52K cathepsin D mRNA by estrogens and antiestrogens has been studied and chromosome localization determined by in situ hybridization. Clinical studies using both immunohistochemistry and immunoenzymatic assay of breast cancer cytosol have shown that the concentration of total cellular cathepsin D (52K + 48K + 34K) is related to the proliferation of mammary ducts and to the prognosis of breast cancer. Its cytosolic concentration in primary tumors of postmenopausal patients is correlated slightly with lymph node invasion and significantly with shorter disease-free intervals in a 6-year retrospective study with the Danish Breast Cancer Groups and Finsen Institute (S. Thorpe et al.).
Cancer research, 1989
In human mammary cancer cells, pro-cathepsin D (pro-Cath-D) is induced by estrogens and 50% of it is secreted. To determine whether its secretion is characteristic of mammary cells or transformed cells, we compared its production, processing, and glycosylation in primary cultures of normal mammary epithelial cells to those found in breast cancer cell lines. The cytosolic concentration of total cathepsin D (precursor and mature enzyme) measured by enzyme-linked immunosorbent assay was 8 times higher in cancer cells. Its mRNA level estimated by Northern blot analysis was 8 to 50 times higher and its secretion was 30 times higher in cancer cells. Using pulse-chase labeling, the cellular processing of pro-Cath-D was altered in hormone-dependent and -independent breast cancer cells in comparison to normal cells. This alteration resulted in a lower accumulation of mature enzyme, while the secretion and cytoplasmic accumulation of pro-Cath-D was greater in breast cancer cells than in norma...
Relation between cathepsin D expression and other prognostic factors in breast carcinomas
Clinical chemistry, 1995
We evaluated cathepsin D concentrations in 318 breast carcinoma specimens with a standardized IRMA and established distribution values of 5.9-217.8 nmol/g (median 51.8). Concentrations of cathepsin D did not correlate with age or with concentrations of HER-2/neu oncoprotein, estrogen receptor, or epidermal growth factor receptors. A significant correlation was observed between cathepsin D and progestin receptor (P = 0.009), but only in postmenopausal patients. In our role as a National Reference Laboratory for conducting interlaboratory comparisons of tumor markers, we evaluated cathepsin D assay proficiency by using control samples with intra- and interassay CVs of 2-8% and 10-13%, respectively. Human reference specimens containing known quantities of cathepsin D were developed to facilitate standardized testing. The IRMA procedure and the use of quality-assurance samples permits evaluation of the clinical significance of cathepsin D in human breast cancer trials.