Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several glycosylated macromolecules associated with normal and malignant pancreatic ductal cells have been described. We have generated a monoclonal antibody, LD-B1, by immunizing Balb/c mice with the postmicrosomal extract of fresh human pancreatic ductal carcinoma tissue and used it in this study to characterize the nature of the target antigen. The antigen detected by LD-B1 antibody was purified to homogeneity by affinity chromatography. Enzymatic and biochemical analysis showed it to be a nonsialylated glycoprotein that on Western blotting and immunoprecipitation analyses had an apparent molecular weight of 300-400 kDa. The mobility on gels was not affected by reducing or denaturing conditions. Competitive inhibition assays with various MoAbs and lectins indicated that the epitope recognized by LD-B1 antibody involves the carbohydrate sequence Gal beta 1----3Gal beta 1----3(or 4)GlcNAc beta 1----3Gal. Using a double determinant sandwich ELISA, elevated antigen levels were detected in the sera of 5 of 6 patients with pancreatic carcinoma, 0 of 3 patients with chronic pancreatitis, and 12 of 137 normal controls. These results suggest that patients with pancreatic carcinoma exhibit altered expression of a heavily glycosylated molecule related to a blood group precursor immunodeterminant.
Exp Mol Pathol 1990 Oct
PMID:Biochemical characterization and serological immunoassay of a pancreatic carcinoma-associated antigen defined by monoclonal antibody LD-B1. 170 61

The aim of this study was to define a cellular antigen associated with human pancreatic ductal carcinoma, and to study its distribution in a large panel of malignant, benign, and normal tissues. For this purpose, monoclonal antibodies were generated against a postmicrosomal fraction of fresh human pancreatic cancer. One such antibody, LD-B1, reacted strongly with 95% of cases of primary and metastatic pancreatic ductal carcinomas. It also immunostained gallbladder carcinomas and cholangiocarcinomas. By contrast, it exhibited focal or weak reactivity to 10% of other types of common malignant tumors. On normal pancreas, staining was observed in ductal and centriacinar cells, but not in acinar or endocrine cells. In chronic pancreatitis, ductal staining intensity increased proportionally with the degree of cellular atypia. The antigen was also detected in gallbladder epithelium, bile ducts, ductal epithelium of sweat glands and salivary glands, and focally in a few other normal nonpancreatic tissues. These results suggest that LD-B1 MoAb can be used in immunohistochemical studies as a marker of pancreatic adenocarcinoma.
Exp Mol Pathol 1990 Oct
PMID:Isolation and immunohistochemical characterization of a pancreatic carcinoma-associated monoclonal antibody. 170 63

The distribution of the myoepithelial cells in 32 cases of ductal carcinoma-in-situ (DCIS) of the breast (11 not associated, 21 associated with invasive carcinoma) was investigated with a recently developed immunoperoxidase method for actin. Actin-rich myoepithelial cells were detected at the periphery of some ducts, however, their presence was neither constant nor continuous. Large areas of DCIS were devoid of a myoepithelial cell layer and the neoplastic cells were directly in contact with the stroma. No differences related to the histological pattern of DCIS or the presence and absence of invasive carcinoma were noted. The behaviour of the myoepithelial cells in ductal carcinoma appears different from that observed in cases of lobular carcinoma (Bussolati 1980) and of cystic disease, and may thus be of diagnostic interest. The selective destruction of myoepithelial cells in cases of DCIS might result in a focal disruption of the basement membrane, thus faciliatating invasion.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Actin-rich (myoepithelial) cells in ductal carcinoma-in-situ of the breast. 610 44

A middle-aged woman without any symptoms of ectopic hormone production underwent a right-sided mastectomy for infiltrating ductal carcinoma. She later developed axillary lymph node metastases which were somewhat carcinoid-like. This prompted further investigation, when scattered argyrophilic endocrine cells were found in both the primary tumour and its metastases. The endocrine cells reacted immunocytochemically with antisera against ACTH and HCG. Despite the endocrine activity of the tumour, it was still regarded as a ductal carcinoma since the endocrine cells constituted the minority cell population. The present study indicates strongly that ectopic hormone production in association with carcinoma of the breast is a result of hormone synthesis and release by the tumour cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Argyrophil endocrine cells with ACTH and HCG immunoreactivity in a carcinoma of the breast. 613 18

We have previously shown that a human mammotropic polypeptide hormone, prolactin (PRL) can act synergistically with steroid hormones to regulate gene expression directed by the long terminal repeat of mouse mammary tumor virus (MMTV LTR) in a human ductal carcinoma cell line T47D cells using a chloramphenicol acetyltransferase reporter gene system and gene transfection methods. In the present study, using various recombinant plasmids we analyzed functional elements in the MMTV LTR that is essential for the PRL responses. We show that the PRL-responsive elements are located in the extreme 5' end of the MMTV LTR, a region previously described by others to be a mammary cell-specific enhancer.
Mol Cell Endocrinol 1993 Oct
PMID:Prolactin acts on the extreme 5' portion of MMTV LTR involving a mammary cell-specific enhancer. 827 23

Growth factor-independent proliferation is an essential aspect of the transformation process. To study the influence of c-erbB-2 overexpression on the autonomous growth of human mammary cancer cells, we used a series of non-neoplastic and neoplastic human mammary epithelial cell lines isolated from a patient with intraductal and invasive ductal carcinoma of the breast. The non-neoplastic cell line, H16N-2, which expresses a normal level (single gene copy) of c-erbB-2, was used for comparison with the neoplastic cell lines. Both the metastatic tumor cell lines, 21MT-1 and 21 MT-2, showed equivalent amplification of the c-erbB-2 gene; however, 21MT-1 cells showed a higher level of c-erbB-2 overexpression. Therefore, the H16N-2, 21MT-2, and 21MT-1 cell series forms a distinct gradient of progressively increasing c-erbB-2 gene expression. Furthermore, the overexpression of c-erbB-2 in the 21MT cell lines was concordant with increases in the constitutive tyrosine kinase activity of p185erb-2 measured in the absence of exogenous growth factors in culture. Normal mammary epithelial cells require both insulin-like growth factor (IGF)-l (or supraphysiological concentrations of insulin) and epidermal growth factor (EGF) to proliferate under serum-free conditions in culture. By contrast, 21MT-2 cells showed a reduced requirement for IGF but still required EGF to proliferate. 21MT-1 cells did not require either insulin or EGF to proliferate. Therefore, the progressive increases in constitutive p185erbB-2, tyrosine kinase activity in the 21MT-2 and 21MT-1 cell lines was directly correlated with IGF independence and combined IGF and EGF independence under defined conditions in culture. Experiments using conditioned media and anti-IGF-1 receptor and anti-EGF receptor neutralizing antibodies showed that the growth-factor independence of the tumor cells did not involve detectable IGF- or EGF-like autocrine activity expressed by the 21MT cells. Furthermore, neu differentiation factor/heregulin, a ligand that indirectly activates p185erbB-2 by direct binding to erbB-3 receptors, potently stimulated the proliferation of the growth factor-dependent H16N-2 cells (which expressed c-erbB-2 and c-erbB-3 but not c-erbB-4) in the absence of both IGF and EGF. Thus, HRG-induced mitogenesis mimicked the autonomous growth seen in the 21MT cells that have the highest level of constitutive p185erbB-2 activation. These data support the hypothesis that the constitutive activation of p185erbB-2 in human mammary carcinoma cells causes growth-factor independence by directly activating multiple signal-transduction pathways that substitute for both IGF and EGF during proliferation.
Mol Carcinog 1996 Mar
PMID:Insulin-like growth factor and epidermal growth factor independence in human mammary carcinoma cells with c-erbB-2 gene amplification and progressively elevated levels of tyrosine-phosphorylated p185erbB-2. 859 35

Retinoids modulate gene activity, cell growth and differentiation by binding to a series of nuclear receptors, i.e., retinoic acid receptors (RARs) or retinoid X receptors. Retinoic acid (RA) inhibition of estrogen receptor (ER)-positive breast carcinoma seems to be mediated through RAR alpha. Estrogens upregulate RAR alpha in ER-positive breast carcinoma cell lines. In this study we examined RAR alpha expression in the ER-positive MCF7 and ER-negative MDA-MB-231 human breast carcinoma cell lines as well as in 10 ER-negative and 9 ER-positive infiltrating ductal breast carcinoma specimens using immunohistochemistry and quantitation by image cytometry. MCF7 cells expressed twofold higher levels of RAR alpha protein than MDA-MB-231 cells. RAR alpha expression, as detected by immunostaining and quantitated by image cytometry, was upregulated in these cells by estradiol. ER-positive breast carcinoma specimens also exhibited approximately two-fold higher RAR alpha levels than their ER-negative counterparts. Thus, RAR alpha expression is significantly elevated in ER-positive breast tumors as assessed by detection and quantitation using immunohistochemical staining and image cytometry, respectively. Whether the decrease in RAR alpha protein levels and loss of RA-mediated growth inhibition in ER-negative tumor plays a role in the increased metastatic potential of ER-negative tumors remains to be determined.
Diagn Mol Pathol 1997 Feb
PMID:Elevated expression of retinoic acid receptor-alpha (RAR alpha) in estrogen-receptor-positive breast carcinomas as detected by immunohistochemistry. 902 36

Carcinoma of the breast is thought to evolve through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. Here lumpectomy specimens from five patients were studied, selected for the presence of ductal hyperplasia without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Laser microdissection of tissue allowed precise sampling and direct correlation of phenotypic and genotypic changes. Analyses of the samples revealed an increasing mean number of chromosomal changes occurring with increasing histologic severity, and for the first time chromosomal abnormalities were demonstrated in ductal hyperplasia without atypia. Chromosomal changes found in each of the four histologic entities included gains on 10q, 12q, 16p, and 20q and loss on 13q. In ductal hyperplasia without atypia, gain on 20q as well as loss on 13q was detected with high frequency (four of five samples). Alterations identified in more than 50% of atypical ductal hyperplasia samples included gains on 3p, 8q, 15q, and 22q and loss on 16q. In ductal carcinoma in situ, gain of DNA on 1q and 17q and loss on 4q were additionally found, and in invasive ductal carcinoma, further gains on 6p, 10q, 11q13, and 17p were identified. The chromosomal alterations occurring in the different histopathologic lesions strongly suggest that these regions harbor tumor suppressor genes or oncogenes significant for the development of ductal carcinoma of the breast.
Diagn Mol Pathol 2000 Mar
PMID:Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer. 1071 8

RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to the proteins encoded by HIV-1 and are expressed by 95% of breast and gynecological cancer cases in women and prostate cancer cases in men. Binding of the monoclonal antibody (MAb) RAK-BrI to cancer RAK antigens has been found to be inhibited by a peptide derived from the variable loop V3 of HIV-1. Since MAb RAK-BrI has been developed against denatured froms of breast cancer proteins, and it binds to a short epitope, GRAF, this MAb does not recognize the native, three-dimensional structure of proteins. Subsequently Western blot, after electrophoretic separation in gels with SDS, has been used to detect these unique cancer markers. The current studies were focused on the immunohistochemical evaluation of the novel marker RAK. Serial sections, 5 microm thick, were cut from frozen or Formalin-fixed, paraffin-embedded tissue blocks and immunostained with MAb RAK-BrI. All of the 53 cases of breast cancer tested RAK positive and no differences were observed in the immunohistochemical staining of lobular and ductal carcinoma cases. In contrast, MAb RAK-BrI antigens were detected in only 3 of 15 cases of macroscopically normal breast removed during mastectomy for breast cancer. It is noteworthy that Western blots of breast samples from the same series demonstrated a high expression of three RAK antigens in 20/20 of invasive breast carcinomas, while there was only a very weak expression of RAK antigens in 2/7 of the macroscopically "normal" breast samples. Due to the suspected viral origin of RAK markers, immunohistochemical staining with MAb RAK-BrI might be a useful tool in the early detection of malignant changes occurring in breast tissues.
Exp Mol Pathol 2000 Aug
PMID:Immunohistochemical versus molecular detection of RAK antigens in breast cancer. 1089 Dec 90

Medullary carcinoma of the breast has attracted attention because of its relatively good prognosis, in spite of its high cytologic grade. It has, by definition, a consistent, florid tumor infiltrating lymphocyte (TIL) population, probably the result of cytotoxic T-lymphocytes recognizing tumor cells in an HLA-DR-restricted manner. HLA-DR tends to be more highly expressed on primary medullary carcinoma cells than on ductal carcinoma cells; however, the MHC-class II antigenicity of the tumor cells themselves has not been analyzed extensively, and as yet there has been no comparative study of HLA-DR expression in medullary and ductal carcinomas metastatic to lymph nodes. Eleven cases of medullary carcinoma and 15 cases of ductal carcinoma, primaries, and respective lymph node metastases were analyzed by immunoperoxidase staining for HLA-DR and lymphocytes antigens. Polymerase chain reaction (PCR) analysis to identify HLA-DR subtypes from the paraffin blocks was performed on selected cases of primaries and nodal metastases of both tumor types. Immunoperoxidase staining for HLA-DR antigen revealed a marked difference in antigen expression between medullary and ductal carcinomas. In the medullary carcinomas, the mean percentage of cells staining for HLA-DR was 74.5% in the primary tumors and 67.3% in the nodal metastases. For the ductal carcinomas, the mean percentage of cells staining was 17.7% in the primaries and 7% in the metastases. There was a tendency for the level of HLA-DR expression to remain high in medullary carcinoma metastatic to nodes, whereas whatever HLA-DR was present within ductal primaries tended to diminish when cells metastasized to regional nodes. PCR analysis of the HLA-DR within the two tumor types revealed no emerging subtype or variant that could be associated with either the medullary or the ductal carcinomas. Medullary carcinoma cells express much greater quantities of HLA-DR, on the whole, than ductal carcinomas. Expression of HLA-DR is retained on medullary carcinoma cells that have spread to lymph nodes, whereas the smaller quantities of HLA-DR present within ductal primaries tend to diminish even further when the tumor cells are found in lymph nodes. No discernible HLA-DR mutations or predominant subtypes emerged on PCR analysis, and the authors therefore conclude that it is the quantity and not the quality of HLA-DR expression in medullary carcinoma that maintains the characteristic TIL infiltrate, not seen in ductal carcinomas.
Appl Immunohistochem Mol Morphol 2001 Sep
PMID:Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases. 1155 51


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