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PubMed1987

Constitutive protein secretion from the exocrine pancreas of fetal rats.

Two general kinds of exocytotic secretion of proteins are known: that which is stimulated by secretagogues; and constitutive exocytosis, which is unable to be stimulated. The exocrine pancreas has often been cited as a model system for the first kind of secretion. However, the release of digestive enzymes from the exocrine pancreas of 1-day prenatal rats cannot be stimulated by secretagogues; therefore, its secretion is constitutive. To gain insight into the intracellular pathways which mediate secretion in the fetal gland, we examined the kinetics of release of newly synthesized proteins. We find that fetal pancreas in a steady state of secretion releases pulse-labeled secretory proteins in two kinetically distinct phases. The first phase occurring during 0-6.5 h of chase comprises approximately 12% of total incorporated radioactivity, the second phase beginning at greater than 7 h of chase comprises the remainder. Based on analysis by electron microscope autoradiography, radiolabel is localized during the first phase of secretion in immature granules/condensing vacuoles, Golgi compartments, and few mature granules. The second phase of secretion occurs when radiolabel is predominantly in mature granules. We propose that secretion occurs via (at least) 2 exocytotic routes, both of which are constitutive in fetal pancreatic tissue.

Animals↗

PubMed1984

Phorbol myristate acetate-stimulated production of interleukin 2 by T-cell lymphoma and constitutive production by derived hybridomas.

To isolate a stable tumor cell line source of IL-2 (TCGF), 19 murine T-cell lines and their derivatives were screened for both constitutive and mitogen-stimulated IL-2 production. The cloned subline of a mouse thymic lymphoma EL-4 designated as EL-4TF could be stimulated with PMA to produce 80 U/ml of IL-2. A TK- EL-4TFR mutant line has been selected from the EL-4TF cell population by treatment with 5-BrdUrd. The EL-4-TFR cells were stimulated with PMA and fused with the cells of thymic lymphoma BW5147. The resulting BH3 hybrid cell population was repeatedly cloned and tested for constitutive IL-2 production: two of the BH3 hybridoma clones were found to produce IL-2 constitutively. The IL-2 of EL-4TF origin was found to support permanent in vitro growth of IL-2 dependent, tumor-specific T killer cell line CTLL when present in culture medium at a concentration of at least 0.1 U/ml. Since the EL-4TF-derived IL-2 preparations were contaminated with PMA, it was of interest whether PMA alone has a growth-promoting activity in CTLL cell cultures. Permanent cultivation of CTLL cells in an IL-2-free medium containing PMA was not possible. However, both mitogenic and co-mitogenic effects of PMA on CTLL cells were observed.

Animals↗

PubMed1983

Interaction of constitutive and phenobarbital-induced cytochrome P-450 isozymes during the sequential oxidation of benzphetamine. Explanation for the difference in benzphetamine-induced hydrogen peroxide production and 455-nm complex formation in microsomes from untreated and phenobarbital-treated rats.

The following pathway for benzphetamine (Bz) metabolism in rat hepatic microsomes was established: Bz leads to norbenzphetamine (NorBz) leads to N-hydroxynorbenzphetamine leads to N-benzylethyl-alpha-phenylnitrone leads to 2-nitroso-1-phenylpropane. The last product forms a complex with cytochrome P-450 with an absorbance maximum at 455 nm. Steps 1, 2, and 4 are cytochrome P-450-dependent; Step 3 appears to involve the flavoprotein, mixed-function amine oxidase. Step 2 is partially uncoupled, producing H2O2 at approximately 3 times the rate of N-hydroxylation. Bz is oxidized to NorBz in microsomes from both untreated rats (U-microsomes) and phenobarbital (PB)-treated rats (PB-microsomes), but the 455-nm peak does not appear in U-microsomes until almost all of the Bz has been converted to NorBz; i.e., Bz inhibits the oxidation of NorBz in U- but not in PB-microsomes. The inhibition is competitive. Bz inhibits the oxidation of the nitrone to 2-nitroso-1-phenylpropane in both U- and PB-microsomes; NorBz inhibits this reaction in U-microsomes only. These results can be explained as follows. The substrate affinities of the cytochrome P-450 primarily responsible for the N-demethylation of Bz in U- and PB-microsomes differ markedly. The constitutive cytochrome(s) in U-microsomes has a high affinity for Bz; PB induces both this form and a cytochrome(s) with a lower affinity for Bz. The substrate affinities of these two cytochromes P-450 for NorBz do not differ appreciably. Thus, although both forms of cytochrome P-450 can oxidize Bz and NorBz in PB-microsomes, Bz is primarily oxidized by the constitutive form, whereas NorBz is oxidized primarily by the induced form, thereby relieving competition and increasing the over-all sequential oxidation of Bz. The nitrone appears to be oxidized exclusively by the constitutive form in both U- and PB-microsomes. The current study shows that PB induction of monooxygenase activity need not be due entirely to an increase in the amount of cytochrome P-450 or the substrate selectivity of cytochrome P-450 isozyme(s) responsible for that activity, but that, in at least one case, the metabolism of Bz, PB-induced activity can be due, at least in part, to the induction of a cytochrome P-450 isozyme that relieves substrate inhibition.

Animals↗

PubMed1981

Constitutive gene expression and restoration of the normal phenotype in malignant cells: a model for the origin and evolution of leukemia.

The change from normal to malignant cells involves a sequence of changes including specific chromosome changes. After this sequence, some leukemias can still be induced to revert with a high frequency from a malignant to a non-malignant phenotype. Results obtained from the analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, restoration of the normal phenotype by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation defective leukemic cell mutants have been used to propose a general model for the origin and evolution of leukemia. The model states that leukemia originates by changing specific pathways of gene expression required for growth from inducible to constitutive, in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways of gene expression can uncouple other controls, which then causes blocks in differentiation and the further evolution of leukemia. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells, can also explain the origin and evolution of other types of malignancies.

Animals↗

PubMed1982

Some thoughts on the constitutionality of good samaritan statutes.

Good samaritan laws provide legal immunity to persons who assist in medical emergencies. Because good samaritan laws eliminate the common law right of victims to secure redress for their injuries, these statutes raise certain constitutional questions. The Article begins by examining the vulnerability of good samaritan statutes to federal constitutional attack on substantive due process and equal protection grounds. It then considers the susceptibility of such laws to state constitutional attack on the same grounds. The Article concludes that while such statutes are not likely to violate federal substantive due process and equal protection provisions, they may be held unconstitutional on similar state grounds.

Emergency Medical Services↗

PubMedDate not supplied

Constitutional aspects of the osteochondroses.

The osteochondroses comprise a heterogeneous group of clinical disorders, the diagnosis of which is generally confirmed by radiologic appearances. The causes are unknown and little pathologic material has been examined to resolve this problem. Moreover, study of the affected bone yields minimal insight into the cause of the disorder because bone cells respond in a set pattern irrespective of the initial injury. Although acute trauma or prolonged abnormal mechanical forces in the region of epiphysis can lead to bone collapse and necrosis, it is unlikely that such forces are sufficient to affect normal healthy bone. The timing, distribution, multiple sites and familial etiology, as well as the close association between osteochondroses and certain congenital disorders, strongly suggest that there is constitutional epiphyseal inadequacy. The daily stresses of healthy childhood activity are enough to compromise the development of constitutionally weak epiphyses. When architectural bone collapses, the full osteochondrotic picture is manifested. Bone compaction can be brought about only by mechanical means and the force needed is inversely proportional to the degree of epiphyseal abnormality, e.g., a mildly dyschondrotic epiphysis will not present clinically without sufficient trauma to produce architectural collapse. Recent anthropomorphic studies have shown that children with Perthe's disease have a generalized growth disorder. Further long-term comprehensive biological studies are needed to provide more data on children suffering from the osteochondroses if the underlying constitutional defects are to be identified.

Biomechanical Phenomena↗

PubMed1980

[Constitutional-somatotopic factors in the clinical picture of alcoholic psychoses and obvious signs of paranoid schizophrenia].

The clinical and anthropometrical methods were used to study the constitutional traits of 240 patients with psychotic forms of alcoholism and 300 patients with paranoid schizophrenia. The somatotypes were assessed by the Rees-Eysenck method. The prepsychotic parameters of alcoholism and the structure of alcoholic delirium were studied in 78 patients, as well as the manifest symptoms of paranoid schizophrenia. The study demonstrated a syndromal modified expressivity in exo- and endogenous processes, depending upon the somatotypical constitution. Simple syndromes were more frequently found in patients with a pyknic somatotype, and complicated in normosthenical and asthenic types of body built. It is suggested that the constitutional and somatotypical factors be included into the multifactorial analysis of the syndrome structure and prognosis in the development of the psychosis.

Adult↗

PubMed1995

Expression of constitutively activated hepatocyte growth factor/scatter factor receptor (c-met) in B16 melanoma cells selected for enhanced liver colonization.

The murine melanoma B16-LS9 cell line was obtained after repeated passages in vivo through the liver of syngeneic mice, and shows an enhanced ability to colonize the liver after intravenous inoculation when compared to its parental, unselected counterpart B16-F1. We have previously shown that paracrine growth effects mainly account for better growth of B16-LS9 in the liver than at other sites, and more recently we reported hepatic transferrin as a factor contributing to efficient growth in the liver. Here we show that increased expression of constitutively activated c-met (the receptor for Hepatocyte Growth Factor/Scatter Factor) consistently occurs during selection of B16 cells through the liver. Constitutive activation of c-met seems to follow its own overexpression and not to depend on an autocrine mechanism. As a consequence, liver-selected B16 melanoma cells have higher tyrosine-kinase activity and higher amounts of tyrosine-phosphorylated proteins than parental B16-F1 or lung-specific B16-F10 cells. Overexpression of constitutively activated c-met enhances motility and invasiveness of B16-LS9 cells, presumably favoring their colonization efficiency in vivo. However, whether levels of c-met expression also determine the organ-specificity of B16 melanoma cells needs further clarification.

Animals↗

PubMed1995

Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.

Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.

Amino Acid Sequence↗

PubMed1993

[Pediatric constitutional therapy].

The basic idea of constitutional medication goes back to ancient times. These experiences were integrated in the western world and in modern times supplemented by new knowledge. Our constitutional medicine has roots in the unique and brilliant idea of "Miasmatic Theories" of Hahnemann and the other famous doctors. We have worked since on 1950 theoretical and practical aspects of constitutional homoeopathic medicine for children.

Child↗

PubMed1995

Constitutive endocytosis and degradation of CD22 by human B cells.

The CD22 B lymphocyte-surface Ag is an important component of the B cell-surface IgM (sIgM)/B cell receptor complex and has been shown to regulate B cell activation. In addition, this molecule has been shown to be an effective target for immunotherapy of B cell malignancies using immunotoxins and radioimmunoconjugates. In this report we describe the internalization and metabolic degradation of this molecule under constitutive conditions and after stimulation of B cells with phorbol dibutyrate or mAbs binding to sIgM, CD19, and CD22. Flow cytometry, "neuraminidase protection," and "neuraminidase shift" assays demonstrated that CD22 is internalized constitutively by unstimulated B cell lines and subsequently degraded in an acidic intracellular compartment (presumably lysosomes) without detectable recycling of the molecule back to the cell surface. Ligation of CD22 with anti-CD22 mAbs markedly increased CD22 internalization but did not affect the rate of intracellular degradation of CD22, suggesting that anti-CD22 mAbs perturb the intracellular trafficking of CD22. In contrast, CD22 internalization and degradation was unaffected by stimulation of B cell lines with phorbol dibutyrate or ligation of other components of the B cell receptor complex (e.g. CD19, sIgM) with mAbs. These patterns of internalization and degradation under constitutive and stimulated conditions contrast with those reported for other lymphoid differentiation Ags (e.g., the TCR, CD3, CD4, and the transferrin receptor), and may help explain the utility of this molecule as a target for immunoconjugate therapy.

Antibodies, Monoclonal↗

PubMed1995

Kronenberg vs. Henry Ford Health System, et al. addresses constitutionality of malpractice reform legislation.

In November 1994, a Wayne County Circuit Court judge rendered an opinion upholding the constitutionality of the 182-day pre-suit notice and waiting requirements under the Malpractice Reform Legislation which became effective April 1, 1994. The Court's opinion is well written and will lend support to other constitutional attacks taking place in other circuit courts. It is expected that the Kronenberg case will be appealed. MSMS legal counsel will monitor this and other cases contesting the constitutionality of the Malpractice Reform Legislation and keep MSMS members apprised.

Humans↗

PubMed1994

Lytic susceptibility of target cells to cytotoxic T cells is determined by their constitutive major histocompatibility complex class I antigen expression and cytokine-induced activation status.

Cytotoxic T-cell lines (TCL) were raised in vitro using stimulator cells with a defined major histocompatibility complex (MHC) mismatch and tested in a cytotoxic chromium-release assay against haemopoietic and non-haemopoietic target cells from the original stimulator. Monoclonal antibody (mAb)-blocking experiments and simultaneous determination of MHC class I, class II, lymphocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) density by quantitative radioimmunometric methods and flow cytometry on target cells demonstrated that lysis was restricted by MHC class I and dependent upon the constitutive MHC class I antigen expression. Measurements showed a high constitutive expression of class I MHC antigens on peripheral blood mononuclear cells (PBMC), but a low one on keratinocytes (K). Also, PBMC were more susceptible to lysis by TCL than K. Interferon-gamma (IFN-gamma) treatment of K resulted in increased MHC class I antigen expression and enhanced lytic susceptibility to TCL. IFN-alpha and tumour necrosis factor-alpha (TNF-alpha) treatment, which did not modulate MHC class I antigen expression on K, did not influence the amount of K lysis either. None of the cytokines tested in this analysis, however, increased the expression of MHC class I, class II, ICAM-1 and LFA-1 on PBMC. Only IFN-gamma pretreatment showed a minimal, statistically significant increase in MHC class I antigen expression. In spite of the minimal effect of IFN-gamma and no effect of IFN-alpha on class I MHC expression, pretreatment of target cells with both cytokines considerably increased their lytic susceptibility. The mechanism of cytokine-induced enhanced lytic susceptibility to TCL was not explained by increased MHC class I, LFA-1 or ICAM-1 expression, since no correlation was found between surface expression of these molecules and lytic susceptibility to TCL. These data demonstrate that: (1) the constitutive density of MHC class I antigens determines the extent of TCL lysis; (2) IFN-gamma, and not IFN-alpha or TNF-alpha controls the amount of K target cell lysis by increasing their MHC class I antigen expression; and (3) IFN-gamma and IFN-alpha control the amount of PBMC target cell lysis by a mechanism independent of MHC class I, ICAM-1 or LFA-1 expression.

Cell Adhesion Molecules↗

PubMed1994

Strain-specific variation in constitutive and inducible expression of MHC class II, class I and ICAM-1 on rat cerebral endothelium.

Strain variation in levels of inducible major histocompatibility complex (MHC) class II expression by rat cerebral endothelium has previously been reported. Using primary cell cultures of rat cerebral endothelium from PVG (RT1c), LEW (RT1l), PVG.LEW (RT1l) and PVG.AGUS (RT1lv?) strains it was determined that variation in levels of inducible MHC class II expression between strains can be accounted for by both cis-acting elements within the MHC region and by trans-acting elements outside the MHC. In addition it was determined that levels of constitutive MHC class I expression varied between PVG (RT1c) and LEW (RT1l) strains which can be attributed to cis-acting elements within the MHC region. Furthermore, while levels of constitutive class I expression vary between PVG (RT1c) and LEW (RT1l) endothelium we could find no difference in the interferon-gamma (IFN-gamma) inducible expression of class I between these two strains. In contrast the inducibility of intercellular adhesion molecule-1 (ICAM-1) in response to IFN-gamma was found to differ between PVG and LEW endothelium. Significant levels of ICAM-1 are induced on LEW cerebral endothelium after 24 hr exposure to 50 U/ml IFN-gamma. However, no significant induction of ICAM-1 could be demonstrated on PVG, or BN cerebral endothelium after the same exposure to IFN-gamma. Induction of ICAM-1 by IFN-gamma precedes MHC class II by at least 24 hr and its persistence is proportional to the concentration of IFN-gamma used. We suggest that the rat MHC region (RT1) contains elements which control the levels of constitutive class I expression and inducible class II expression in response to IFN-gamma, but that other non-RT1 genes influence the inducibility of MHC class II on rat cerebral endothelial cells. This observation, together with the finding that ICAM-1 expression is not significantly increased in response to IFN-gamma on PVG or BN endothelium, suggests that IFN-gamma responsiveness by these strains differs from LEW.

Animals↗

PubMed1994

The polypeptide diazepam-binding inhibitor and a higher affinity mitochondrial peripheral-type benzodiazepine receptor sustain constitutive steroidogenesis in the R2C Leydig tumor cell line.

The polypeptide diazepam binding inhibitor (DBI) and drug ligands for the mitochondrial peripheral-type benzodiazepine receptor (PBR) have been shown to regulate cholesterol transport, the rate-determining step in steroidogenesis, in hormone-responsive steroidogenic cells including the MA-10 Leydig tumor cells. The present study was designed to characterize the role of DBI and PBR in the R2C rat Leydig tumor constitutive steroid-producing cell model. Both DBI and PBR were present in R2C cells. R2C cell treatment with a cholesterol-linked phosphorothioate oligodeoxynucleotide antisense to DBI, but not sense, resulted in the reduction of DBI levels and a concomitant dramatic decrease of the amount of progesterone produced. These observations strongly suggested that DBI was important in maintaining constitutive steroidogenesis in R2C cells. Radioligand binding assays revealed the presence of a single class of PBR binding sites with an affinity 10 times higher (Kd approximately 0.5 nM) than that displayed by the MA-10 PBR (Kd approximately 5 nM). Photolabeling of R2C and MA-10 cell mitochondria with the photoactivatable PBR ligand [3H]1-(2-fluoro-5-nitrophenyl)-N-methyl-N-(1-methyl-propyl)-3- isoquinolinecarboxamide showed that the M(r) 18,000 PBR protein was specifically labeled. This indicates that the R2C cells express a PBR protein which has properties similar to the MA-10 PBR. Chemical crosslinking studies of purified metabolically radiolabeled DBI to mitochondria provided direct evidence that DBI specifically binds to the M(r) 18,000 PBR protein. Moreover, DBI and a PBR synthetic ligand were able to increase steroid production in isolated R2C cell mitochondria which express the 5 nM affinity receptor. However, mitochondrial PBR binding was increased by 6-fold upon addition of the post-mitochondrial fraction, suggesting that a cytosolic factor modulates the binding properties of PBR in R2C cells and is responsible for the 0.5 nM affinity receptor seen in intact cells. In conclusion, these data demonstrate that DBI plays a key role in maintaining R2C constitutive steroidogenesis by binding to the mitochondrial higher affinity PBR which promotes a continuous supply of cholesterol to the inner mitochondrial side chain cleavage cytochrome P450.

Animals↗

PubMed1993

Infection with human T-lymphotropic viruses leads to constitutive expression of leukemia inhibitory factor and interleukin-6.

Leukemia inhibitory factor (LIF), similar to interleukin-6 (IL-6), is a glycoprotein growth factor and differentiation regulator that has pleiotropic activity in several cellular systems. Recent reports of constitutive IL-6 production from spontaneously proliferating cells from human T-cell leukemia virus (HTLV)-infected individuals led us to examine the expression of IL-6 and LIF during HTLV infection. In vitro infection of peripheral blood lymphocytes with HTLV-I was associated with production of both soluble LIF and IL-6 in conjunction with the increasing HTLV antigen concentration. Northern blot analysis of T-cell lines generated from individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II (Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression of LIF and IL-6 transcripts, as compared with uninfected cell lines (HuT-78, Jurkat). The constitutive expression of LIF and IL-6 was independent of presence of IL-2 in the culture medium, as both IL-2-independent (MT-2, HuT-102, SP, Mo-T) and IL-2-dependent (FS, EG, H2A, H2E) cell lines expressed LIF and IL-6 transcripts. Furthermore, LIF and IL-6 RNA expression in an HTLV-I-infected cell line (MT-2) was enhanced by phorbol ester stimulation via mechanisms that appear to be dependent on the posttranscriptional regulatory controls. These results show that both LIF and IL-6 are produced by HTLV-I- and HTLV-II-infected cells, which could potentially alter the transcriptional regulation of HTLV gene expression by inducing certain early response genes.

Cell Line↗

PubMed1994

Genetically engineered proinsulin constitutively processed and secreted as mature, active insulin.

The conversion of human proinsulin to insulin occurs only in specialized cells which contain the appropriate processing enzymes. To allow proinsulin processing to occur in a wide variety of cell types, we engineered human proinsulin to be cleaved in the constitutive secretory pathway. Using site-directed mutagenesis, we have introduced furin consensus cleavage sequences (Arg-X-Lys-Arg) into the human proinsulin cDNA. These mutations allowed for efficient proteolytic maturation of human proinsulin to insulin within cells containing only a constitutive pathway of secretion. Additionally, a naturally occurring mutation (histidine B10 to aspartic acid) yields a form of human insulin which accumulates 10- to over 100-fold more mature insulin when compared to the mutants lacking this change. Engineering furin-specific cleavage sites into each junction of the human proinsulin cDNA results in the secretion of peptides that display the expected molecular weights for the A and B chains of insulin. The accumulation of mature, processed, human insulin was measured in the supernatants by radioimmunoassay, and the bioactivity of this molecule was measured by its ability to stimulate autophosphorylation of the insulin receptor. Our results suggest that any cell type might be engineered to produce mature, active, and stable insulin in the constitutive pathway of secretion.

3T3 Cells↗

PubMed1994

Predisposition for breast cancer in carriers of constitutional translocation 11q;22q.

A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted us to study the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases was significantly higher than expected among the translocation carriers (P < .001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer.

Breast Neoplasms↗