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Biomedical subjects

D Yee

Publications and source records attributed to D Yee.

At least 55 records · Page 3Linked to original sources
PubMed1997

Lac repressor inducible gene expression in human breast cancer cells in vitro and in a xenograft tumor.

We have studied the lac repressor (lacR) system in two breast cancer cell lines, MCF-7 and MDA-MB-231, in vitro and in vivo. Breast cancer cell lines were stably transfected with lacR and tested for inducibility by transient transfection with a lac operator/luciferase reporter plasmid. The level of expression of lacR did not appear to correlate with the basal or maximal activation of induction by isopropyl beta-D-thiogalactoside (IPTG). Stable transfection with the same reporter gene resulted in up to 40-fold (MDA-MB-231) and 50-fold (MCF7) induction. In the absence of IPTG, a low level of basal reporter gene expression was seen in all clones. Detailed analysis showed that induction was rapid (maximal at 24 h), reversible (a return to basal expression by 24 h) and dose-dependent. To test if this system was also inducible in vivo, cells were grown as a xenograft tumor in nude mice. Mice were given IPTG (0.53 mmol) by intraperitoneal injection, and the tumors were biopsied at several time points following administration. IPTG caused a 10-fold increase in luciferase activity after 8 h, which persisted for 24 h. Thus, this system allows tightly controlled inducible in vivo and in vitro gene expression with low basal expression, and it may provide an important tool for the study of lethal genes in human breast cancer cells.

Animals↗
PubMed1997

Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival.

Insulin-like growth factors (IGFs) interact with specific cell surface receptors to mediate cell growth. Intracellular effects of the IGFs are mediated by activation of secondary messenger molecules. One of these proteins, insulin receptor substrate-1 (IRS-1), is phosphorylated after type I IGF receptor activation and has a major role in IGF signaling. Receptor activation also is influenced by high-affinity IGF binding proteins (IGFBPs). In serum, IGFBP-3 is the predominant species. The role of IGFBP-3 in the regulation of breast cancer cell growth is unclear; both growth inhibition and stimulation have been documented in tissue culture systems. To investigate the influence of IGFBP-3 and IRS-1 in breast cancer, we measured levels of these proteins by ELISA and immunoblotting in 195 node-negative primary human breast cancers and compared their levels with known prognostic factors and disease-free survival (DFS). IGFBP-3 levels correlated positively with tumor size (r = 0.27, P < 0.0001) and negatively with estrogen receptor (r = -0.35, P < 0. 0001) and progesterone receptor (r = -0.16, P = 0.021). In contrast, IRS-1 did not correlate with prognostic factors, but higher levels of IRS-1 predicted worse DFS for the subset of patients with tumors </=2 cm (P = 0.04), and for patients with estrogen receptor-positive tumors, there was a trend toward worse DFS (P = 0.06). These results suggest that higher tumor levels of IGFBP-3 are associated with worse features in breast cancer. However, IGFBP-3 was not an independent prognostic factor. In contrast, high levels of IRS-1 in the tumors predicted a higher incidence of recurrence, suggesting that IRS-1-mediated signaling in breast tumors may be involved in the growth regulation of breast cancer.

Breast Neoplasms↗
PubMed1996

Sensitivity and selectivity in protein similarity searches: a comparison of Smith-Waterman in hardware to BLAST and FASTA.

To predict the functions of a possible protein product of any new or uncharacterized DNA sequence, it is important first to detect all significant similarities between the encoded amino acid sequence and any accumulated protein sequence data. We have implemented a set of queries and database sequences and proceeded to test and compare various similarity search methods and their parameterizations. We demonstrate here that the Smith-Waterman (S-W) dynamic programming method and the optimized version of FASTA are significantly better able to distinguish true similarities from statistical noise than is the popular database search tool BLAST. Also, a simple "log-length normalization" of S-W scores based on the query and target sequence lengths greatly increased the selectivity of the S-W searches, exceeding the default normalization method of FASTA. An implementation of the modified S-W algorithm in hardware (the Fast Data Finder) is able to match the accuracy of software versions while greatly speeding up its execution. We present here the selectivity and sensitivity data from these tests as well as results for various scoring matrices. We present data that will help users to choose threshold score values for evaluation of database search results. We also illustrate the impact of using simple-sequence masking tools such as SEG or XNU.

Computers↗
PubMed1996

Loss of either CD4+ or CD8+ T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS.

Normal mice readily survive a sublethal intradermal (i.d.) infection with Francisella tularensis live vaccine strain (LVS), a model intracellular bacterium, and are strongly protected against subsequent lethal challenge. However, athymic nu/nu mice, which lack mature alphabeta TCR+ T lymphocytes, succumb to i.d. infection within 30 days. Here we characterize the alphabeta T cell subpopulations necessary for both resolution of i.d. infection and generation of optimal protective immunity to LVS. BALB/cByJ mice treated with anti-CD4 or anti-CD8 Abs before i.d. infection survived and cleared bacteria, and anti-CD4- or anti-CD8-treated immune mice survived a very strong i.p. challenge of 10,000 LD50s. Among mutant mice with targeted gene disruptions (knockouts), CD4-, beta2-microglobulin-deficient (which are also CD8-), and gammadelta TCR- mice all resolved a large sublethal i.d. infection. All CD4- and beta2-microglobulin-deficient mice readily survived subsequent lethal i.p. challenge of 10,000 LD50s, even in the absence of specific IgG Abs, as did most (86%) gammadelta TCR- mice. In contrast, alphabeta TCR- mice or alphabeta + gammadelta TCR- mice died about 35 days after i.d. infection. Depletion of gammadelta+ T cells from alphabeta TCR- mice had no effect on mean time to death from i.d. LVS infection. Therefore alphabeta TCR+ cells are required for protection, but either CD4+ or CD8+ T cells are individually sufficient to resolve a large sublethal i.d. LVS infection and to protect against a maximal secondary lethal challenge. These results emphasize the remarkable plasticity of the alphabeta T cell response in protective immunity to intracellular bacteria.

Animals↗
PubMed1996

Adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase in an ascites model of human breast cancer.

In this study, the growth of locally disseminated breast cancer was modeled using a human breast cancer cell line, MDA-MB-435A, adapted to grow as an ascites tumor in athymic mice. Ex vivo infection of MDA-MB-435A cells with adenovirus containing the herpes simplex virus thymidine kinase gene (HSV-tk) were injected into the intraperitoneal cavity of athymic mice. Ganciclovir (GCV) treatment resulted in prolonged median survival (117 vs. 34 days, p < 0.001) compared to untreated or control animals. Adenovirus containing HSV-tk also demonstrated therapeutic activity after in vivo transduction resulting in prolongation of median survival after GCV treatment (32 vs. 25 days, p < 0.001). However, compared to ex vivo treatment, the effect was modest. In an attempt to increase survival, the viral dose was increased three-fold. Instead of prolonging survival, the increased dose resulted in more toxic deaths. Necropsy demonstrated that the most significant histologic abnormality was marked, diffuse, cytomegalic changes in the liver. Polymerase chain reaction (PCR) analysis of hepatic DNA demonstrated the presence of the virus in the affected tissue. Similar host toxicity and hepatic abnormalities were seen in non-tumor-bearing mice treated with ADV/RSV-tk plus GCV. In conclusion, adenoviral vectors can successfully transfer genes in vivo to cancer cells growing as ascites tumors. Transduction with HSV-tk followed by GCV treatment can prolong survival in this model system of disseminated disease, however toxicity can be substantial. Further refinement in targeting expression of HSV-tk will be required to enhance the therapeutic benefit.

Adenoviridae↗
PubMed1996

Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: detection of higher levels in tumors with poor prognostic features.

BACKGROUND: The insulin-like growth factor (IGF)-binding proteins (IGFBPs) regulate the actions of the IGFs by influencing interactions between the IGFs and the IGF receptors. IGFBP-3, one of the six known species of IGFBPs, is the predominant IGFBP in serum and is expressed by breast cancer cells. Compared with estrogen receptor (ER)-positive samples, ER-negative breast cancer cell lines and tumors express higher levels of IGFBP-3. Therefore, expression of IGFBP-3 may be relevant in breast cancer biology, although it is unknown whether IGFBP-3 levels correlate with other breast cancer prognostic factors besides ER status. It is also not known how different methods used to measure IGFBP-3 in breast cancer correlate. PURPOSE: We measured IGFBP-3 messenger RNA (mRNA) and protein levels in breast tumors by different methods to test how these methods compare and to investigate the relationship between IGFBP-3 and breast cancer prognostic factors. METHODS: We analyzed 40 human breast tumors and examined IGFBP-3 expression by ligand blot analysis, immunoblot analysis, immunoradiometric assay (IRMA), and ribonuclease protection assay. Another set of 40 breast tumors, selected according to ER and progesterone receptor (PR) status, S phase, and ploidy, was analyzed by IRMA. RESULTS: In 26 (65%) of 40 samples in which RNA could be isolated, IGFBP-3 mRNA levels correlated with IGFBP-3 levels measured by IRMA (two-sided; P = .0001) but not with IGFBP-3 levels measured by ligand blot or immunoblot. Protein levels were highly correlated among all protein assays. Because the IRMA was more sensitive and accurate than the ligand blot and immunoblot assays, we used IRMA to examine IGFBP-3 levels in an additional 20 primary breast tumors with poor prognostic features (ER and PR negativity, high S phase, and aneuploidy) and in 20 tumors with good prognostic factors (opposite features). IGFBP-3 levels were threefold higher in tumors with poor prognostic features (mean +/- standard deviation = 32.8 +/- 25.2 versus 11.8 +/- 9.7 ng/mg; two-sided; P = .003). CONCLUSIONS: These findings suggest that in human breast cancer, IGFBP-3 mRNA and protein levels are correlated and higher levels of IGFBP-3 are detectable in tumors with poor prognostic features. IMPLICATIONS: IGFBP-3 may be involved in the regulation of breast cancer cell growth.

Aneuploidy↗
PubMed1996

Pharmacokinetic profile of recombination human insulin-like growth factor binding protein-1 in athymic mice.

Neutralization of insulin-like growth factor action by insulin-like growth factor binding protein-1 inhibits the in vitro growth of breast cancer cells. We performed this study to determine the pharmacokinetic profile of recombinant human IGFBP-1 (rhIGFBP-1) in athymic mice as a prelude to testing this protein in a human tumor xenograft model. After the subcutaneous injection of 1 mg, rhIGFBP-1 migrating at 29 kDa could be detected by ligand blotting and immunoblotting. Plasma concentrations of rhIGFBP-1 were quantified by immunoassay and demonstrated a half-life was 2.49 hours with the maximal concentration of 43.5 micrograms/mL occurring at 1 hour. The area under the concentration-time curve was 78.32 micrograms x hr/mL. Plasma clearance was 12.77 mL/hr and the mean residence time was 1.96 hours. rhIGFBP-1 was also detected in some tissues and was also cleared rapidly. These results show that high plasma and tissue levels of rhIGFBP-1 can be obtained after subcutaneous injection in athymic mice, however, the short half-life of the protein may limit its therapeutic use.

Animals↗
PubMed1996

Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cells.

IGF-I regulates renal growth and development. Insulin-like growth factor binding proteins (IGFBPs) are synthesized by the kidney and may modulate the local autocrine and/or paracrine actions of IGF-I. We have previously demonstrated that mesangial cells (MC) release IGF-I and IGF-binding activity; however, the specific IGFBPs produced by these cells and the factors involved in their regulation are unknown. We examined MC for expression of IGFBP-1 to -6 mRNAs and proteins. RNase protection assays using total RNA demonstrated that MC express all of the IGFBPs. [125I]IGF-I Western ligand blot of conditioned medium demonstrated that MC release IGFBPs of 24, 29, 32 kDa, and a doublet at 46 kDa, consistent with IGFBP-4, -5, -2 and -3, respectively. IGFBP species of 28 and 34 kDa were also detected. Since IGF-I and TGF-beta are implicated in glomerular hypertrophy and matrix expansion, we tested their effect on IGFBPs released by MC. IGF-I (100 ng/ml), TGF-beta (2 ng/ml) and forskolin (10(-5) M) differentially regulated the abundance of IGFBPs released in the conditioned medium in a time-dependent manner. IGF-I and TGF-beta were potent inducers of the release of IGFBP3 protein; however, TGF-beta, but not IGF-I, increased IGFBP3 mRNA levels. Recombinant IGFBP3 was tested for its effect on IGF-I-induced mitogenesis. IGFBP3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner with a peak effect observed at 50 nM IGFBP3. Although TGF-beta is a potent inhibitor of IGF-I-stimulated DNA synthesis, this effect is not mediated via IGFBPs. Expression of IGFBP-1 to -6 by MC suggests that these proteins may modulate IGF-I bioavailability in the glomerulus. IGF-I itself, TGF-beta and cAMP agonists may indirectly modulate the effects of IGF-I via the release of IGFBPs by MC.

Colforsin↗
PubMed1996

Characterization of insulin-like growth factor-I and its receptor and binding proteins in transected nerves and cultured Schwann cells.

The insulin-like growth factors (IGFs) are trophic factors whose growth-promoting actions are mediated via the IGF-I receptor and modulated by six IGF binding proteins (IGFBPs). In this study, we observed increased transcripts of both IGF-I and IGF-I receptor after rat sciatic nerve transection. Schwann cells (SCs) were the main source of IGF-I and IGFBP-5 immunoreactivity until 7 days after nerve transection, when invading macrophages in the distal nerve stumps were strongly IGF-I positive. In vitro, IGF-I promoted SC mitogenesis. Northern analysis revealed that SCs expressed IGF-I receptor and IGFBP-5. IGF-I treatment increased the intensity of IGFBP-5 without affecting gene expression. Des(1-3)IGF-I, an IGF-I analogue with low affinity for IGFBP, had no such effect. Incubation of recombinant human IGFBP-5 with SC conditioned media revealed IGF-I protection of IGFBP-5 from proteolysis, implying the presence of an IGFBP-5 protease in SC conditioned media. Collectively, these data support the concept that, in response to nerve injury, invading macrophages produce IGF-I and SC express the IGF-I receptor, to facilitate regeneration. This regenerative process may be augmented further by the ability of SC to secrete IGFBPs, which in turn may increase local IGF-I bioavailability.

Animals↗
PubMed1996

Minimal requirements for murine resistance to infection with Francisella tularensis LVS.

Intraperitoneal or intravenous infection of mice with Francisella tularensis LVS is lethal, with an intraperitoneal 50% lethal dose (LD50) approaching a single bacterium. Intradermal (i.d.) LVS infection has a much higher LD50, about 10(6) bacteria in BALB/cByJ mice, and survival of i.d. infection leads to solid generation of immunity against lethal challenge. To define the minimal requirements for both initial and long-term survival of i.d. infection, we characterized the nature of i.d. LVS infection in lymphocyte-deficient BALB/cByJ.scid (scid) mice. scid mice infected i.d. with strain LVS survived for about 20 days and then died from overwhelming disseminated infection. However, scid mice treated with monoclonal antibodies to gamma interferon, tumor necrosis factor alpha, or neutrophils-granulocytes all died within 1 week of infection, indicating that these were essential for early control of infection. Studies using GKO (gamma interferon knockout) mice emphasized that gamma interferon is absolutely required for initial survival of i.d. LVS infection. scid mice could be reconstituted for long-term survival of i.d. LVS infection and clearance of bacteria by intravenous transfer of splenic lymphocytes or purified B220-/T+ lymphocytes but not nu/nu lymphocytes. T cells are therefore required for long-term clearance and survival of i.d. LVS infection; efforts to determine whether CD4+ T cells, CD8+ T cells, or both are involved are ongoing.

Animals↗
PubMed1996

Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells.

IGF-I and -II play an important role in regulating bone formation. Bone marrow stromal cells, particularly those with osteoblast-like features, may act in concert with osteoblasts to increase IGF-I and -II levels in the bone microenvironment. Local bioavailability of IGFs, however, is modulated by IGF binding proteins (IGFBPs). We have previously demonstrated that murine TC-1 stromal cells constitutively secrete IGF-I and IGFBPs. In the present study, we determined the phenotype of these cells and used them as a model to explore the effect of IGFBPs on IGF-I-induced mitogenesis. The effect of IGF-I on IGFBPs expressed by TC-1 was also determined. When grown under conditions that promote osteogenic differentiation, TC-1 cells showed high alkaline phosphatase activity and mRNA levels, weakly expressed osteocalcin mRNA, and formed mineralized bone-like nodules. TC-1 cells expressed IGF-I and IGF-II mRNAs, while other stromal phenotypes preferentially expressed IGF-I. IGF-I stimulated TC-1 DNA synthesis in a dose-dependent manner and this effect was inhibited by recombinant IGFBP-1 and -4. Since IGF-I may regulate IGFBP production, the effect of IGF-I on IGFBPs expressed by TC-1 cells was determined. IGF-I increased the abundance of IGFBP-3, -4 and -5 in TC-1 conditioned medium; this correlated with induction of IGFBP-3 mRNA, but not with that of IGFBP-4 or -5 mRNAs. The findings demonstrate that most stromal cells express IGF-I which may act in an autocrine and/or paracrine fashion. The local effects of IGF-I, however, may be blocked by IGFBP-1 or -4. IGF-I regulates the relative abundance of IGFBPs in stromal cells which, in turn, may influence IGF-I-mediated effects on bone remodeling.

Alkaline Phosphatase↗
PubMed1996

Schools, families, and early adolescents: what are we doing wrong and what can we do instead?

Although most individuals pass through adolescence without excessively high levels of "storm and stress," many individuals experience difficulty during this period. Why? Is there something unique about this developmental period that puts individuals at greater risk for difficulty? This paper focuses on these questions and advances the hypothesis that some of the "negative" psychological and behavioral changes associated with adolescent development result from a mismatch between the needs of developing adolescents and their experiences at school and at home. It provides theoretical and empirical examples of how this mismatch develops, how it is linked to negative age-related changes in early adolescents' motivation, self-perceptions, self-evaluations, and psychological competence, and how we could provide more developmentally appropriate social environments, particularly at school.

Adolescent↗
PubMed1995

Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype.

Gene targeting was used to create a null allele at the epidermal growth factor receptor locus (Egfr). The phenotype was dependent on genetic background. EGFR deficiency on a CF-1 background resulted in peri-implantation death due to degeneration of the inner cell mass. On a 129/Sv background, homozygous mutants died at mid-gestation due to placental defects; on a CD-1 background, the mutants lived for up to 3 weeks and showed abnormalities in skin, kidney, brain, liver, and gastrointestinal tract. The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities.

Abnormalities, Multiple↗
PubMed1995

Insulin-like growth factors and breast cancer.

Several years of research have indicated that the insulin-like growth factor (IGF) family of ligands, receptors and binding proteins are expressed in human breast cancer. The ligands are potent mitogens for breast cancer cell lines, and blockade of IGF signaling inhibits tumor growth. The IGFs can be regulated in normal and neoplastic tissue, indicating their important role in proliferation. For example, estrogen, a hormone important in the growth and progression of breast cancer is able to alter expression of IGF ligands, receptors and binding proteins. In addition, recent data now indicate that IGF ligands can also activate estrogen receptor (ER) in a ligand-independent manner. The apparent cross-talk between IGF and ER signaling is especially important to consider since anti-estrogens, such as tamoxifen, are a major modality for the treatment of breast cancer. Recent data suggest that IGFs may also be involved in tamoxifen resistance, through upregulation of the IGF-I receptor. Thus blockade of IGF signaling in combination with tamoxifen may prove to be a beneficial treatment for breast cancer patients.

Breast Neoplasms↗
PubMed1995

Characterization of insulin-like growth factor binding proteins (IGFBP) and regulation of IGFBP-4 in bone marrow stromal cells.

Bone marrow stromal cells synthesize and secrete insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBP). IGFBPs may modulate the action of IGF-I or IGF-II on haemopoiesis. However, the specific IGFBPs produced by various stromal cell types have not been identified. We examined six different stromal phenotypes for IGFBP protein and IGFBP-1 to -6 mRNA expression. [125I]IGF-I ligand blot analysis of conditioned medium demonstrate different patterns of IGFBP secretion by each cell type. The most prominent IGFBPs were 24 and 29 kD species, consistent with IGFBP4 and IGFBP5, respectively. RNase protection assays demonstrate that, overall, stromal cells express IGFBP-2 to -6 mRNAs, with IGFBP4, IGFBP5 and IGFBP6 mRNAs predominating. Since agents that modulate cAMP levels may influence haemopoiesis via the release of stromal-derived cytokines, we determined the effect of forskolin, a cAMP agonist, on IGFBP4 expression in TC-1 cells. Forskolin (10(-5) M) up-regulated IGFBP4 mRNA and protein secretion in a time-dependent manner. These findings suggest that IGFBP-4, -5 and -6 released by stromal cells may be key modulators of the haemopoietic response to IGFs. Release of IGFBP4 by agents that increase cAMP may be an important mechanism involved in regulating IGF bioavailability in the marrow microenvironment.

Animals↗
PubMed1995

Proliferation of cultured human prostate cancer cells is inhibited by insulin-like growth factor (IGF) binding protein-1: evidence for an IGF-II autocrine growth loop.

In this study, we examined the expression of insulin-like growth factor (IGF) ligands, receptors, (IGFR1, IGFR2), and binding proteins (IGFBPs) in the human prostate cancer cell line DU145, as well as its mitogenic response to the IGFs. Using RNase protection assays, we found expression of IGF-II, IGFR1, and IGFR2 but failed to detect IGF-I messenger RNA. Distinct binding protein species as well as immunoreactive IGF-II were detected in conditioned media using radioligand and immunoblotting assays. Compared with controls, treatment with exogenous IGF-I and IGF-II resulted in stimulation of monolayer and anchorage-independent growth. Recombinant human IGFBP-1, which binds IGF-II with high affinity, inhibited IGF-II-induced monolayer growth and both baseline and IGF-II-induced anchorage-independent growth in this cell line. Our data suggest IGF-II is as an autocrine growth factor in DU145 cells, and that inhibition of IGF-II-dependent growth of human prostate cancer cells may represent a new therapeutic strategy for this disease.

Blotting, Western↗
PubMed1994

Prognostic significance of insulin-like growth factor-binding protein expression in axillary lymph node-negative breast cancer.

BACKGROUND: Cellular proliferation, as measured by S-phase fraction, is an important predictor of breast cancer prognosis. The insulin-like growth factors (IGFs) have been shown to regulate proliferation in both normal and neoplastic cells by interacting with specific cell surface receptors. In addition to these receptors, high-affinity extracellular binding proteins also modulate IGF action. These insulin-like growth factor-binding proteins (IGFBPs) could influence breast cancer growth and, like other biological parameters of proliferation, could be related to prognosis. PURPOSE: To test whether IGFBP expression was related to other biological parameters and disease-free survival, we measured IGFBP expression in 238 lymph node-negative primary breast cancer specimens. METHODS: Proteins were extracted from breast cancer specimens and analyzed by semiquantitative IGF-I ligand blotting for IGFBP expression. IGFBP expression levels were compared to tumor size, age, S-phase fraction, DNA ploidy, and estrogen and progesterone receptor expression by Spearman correlation. RESULTS: Binding protein (BP)-2, BP-3, BP-4, and BP-5 were identified in breast cancer extracts. Estrogen receptor expression was positively correlated with BP-2 (Spearman correlation coefficient, rs = .262; P = .0001), BP-4 (rs = .313; P = .0001), and BP-5 (rs = .242; P = .0002). Similar correlations between progesterone receptor and BP-2, BP-4, and BP-5 were also found. BP-3 was inversely correlated with age (rs = -.251, P = .0001). BP-4 was weakly inversely correlated with tumor size (rs = -.141; P = .0295) and S-phase fraction (rs = -.216; P = .0025). Since tumor size and S-phase fraction are powerful predictors of prognosis in node-negative breast cancer, we examined the value of BP-4 as a predictor of disease-free survival. When stratified by tumor size, patients with large (> 2 cm) tumors that expressed low levels of BP-4 had improved survival when compared with patients with large tumors and high BP-4 levels (P = .001). CONCLUSIONS: IGFBPs can be detected in breast cancer specimens, and their level of expression correlates with other known biological parameters of breast cancer. Large tumors with low levels of BP-4 have relatively favorable prognoses. IMPLICATIONS: These data suggest that the IGFBPs may play a role in breast cancer biology and that BP-4 levels, analyzed in conjunction with tumor size, may have prognostic significance.

Breast Neoplasms↗