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PubMed1999

Insulin-like growth factor I regulates renal development in rodents.

Blocking the action of insulin-like growth factor I (IGF I) impairs kidney development in vitro. However, no renal developmental abnormalities have been reported in newborn transgenic mice that do not express IGF I (Igf1-/-) mice. Ninety-five percent of Igf1-/- mice die immediately following birth. Kidney development continues following birth in rodents. To readdress the question of the participation of IGF I in the process of kidney development, we measured nephron numbers in developed kidneys from Igf1-/- mice that survived past birth, and using a second model of kidney development, characterized the effect of IGF I infused into rat hosts on the renal function of transplanted metanephroi. Igf1-/- mice were born with grossly normal kidneys. At 77 +/- 10 days after birth, Igf1-/- mice that survived were approximately 28% the weight of wild-type (WT) littermates and had proportionally smaller kidneys. The number of nephrons per kidney was reduced by approximately 20% in Igf1-/- mice. Glomerular size was also reduced in Igf1-/- mice. In untreated host rats, neither the size nor inulin clearance of transplanted metanephroi changed significantly from 12-28 weeks postimplantation. The administration of IGF I to hosts did not affect the size of transplanted metanephroi measured at 12-16 weeks following implantation. However, inulin clearances were increased significantly by the administration of IGF I to hosts. Our findings 1) indicate that IGF I plays a role in determining nephron number, 2) suggest that it enhances function in developing kidneys, and 3) establish the potential for the pharmacological use of IGF I to enhance the growth and function of transplanted metanephroi.

Animals↗

PubMed1995

Effects of growth factors on phosphatidylinositol-3 kinase in astroglial cells.

Growth factors differently regulate astroglial cell differentiation and proliferation. In an effort to understand the early intracellular events promoted by growth factors in astroglial cells, we have determined the effects of insulin-like growth factor I (IGF1), insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and fibroblast growth factors (FGFs) on phosphatidylinositol-3 kinase (PI(3)-kinase). In astroglial cells cultured in serum-free medium, IGF1, PDGF, and EGF, which stimulate cell proliferation, increased PI(3)-kinase activity immunoprecipitated with anti-phosphotyrosine antibodies as shown by thin layer chromatography and high performance liquid chromatography. FGFa and FGFb, which strongly stimulate proliferation, glutamine synthetase, and deiodinase activities and modify cell morphology, have no effect on PI(3)-kinase activity. Addition of 1 nM PDGF, 10 nM IGF1, or 100 nM EGF to the culture medium rapidly stimulated PI(3)-kinase activity which declined slowly after 2 min. The stimulation of PI(3)-kinase increased with growth factor concentration. The maximum increase in PI(3)-kinase activity occurred with 50 nM IGF1, 1 nM PDGF, or 100 nM EGF. Since insulin was active only at high concentration (1 microM), its effect was probably mediated through IGF1 receptors and not through insulin receptors. IGF1 and PDGF, to a lesser degree, also increased the PI(3)-kinase activity associated with pp60c-src protein. Immunoblots performed with an antibody directed against the p85-subunit of the PI(3)-kinase confirmed that IGF1 increased the number of PI(3)-kinase molecules associated with phosphotyrosine-containing proteins or with c-src protein. Each growth factor affects in a different manner the association of PI(3)-kinase with phosphotyrosine-containing proteins and with pp60c-src and thus probably modulates intracellular signals downstream of PI(3)-kinase in astroglial cells.

Animals↗

PubMedDate not supplied

Aromatase activity in granulosa cells: regulation by growth factors.

This study describes the effects of insulin, insulin-like growth factor 1 (IGF1), and epidermal growth factor (EGF) on the aromatase activity of granulosa cells isolated from immature rat ovaries. None of the growth factors alone influenced the basal level of aromatase activity, but did modulate follicle-stimulating hormone (FSH)-induced aromatase activity. Insulin and IGF1 augmented the action of a sub-optimal concentration of FSH (5 ng/mL) on aromatase activity in a dose-dependent manner. In contrast, EGF (1-10 ng/mL) was effective in inhibiting aromatase activity maximally stimulated by FSH. Since insulin and IGF1 had opposing actions to those of EGF on FSH-induced aromatase activity, we examined the interactions between the growth factors. EGF inhibited the actions of both FSH and insulin on aromatase activity. Both IGF1 and EGF increased the [3H]thymidine incorporation into the DNA of bovine granulosa cells in vitro, IGF1 being a more potent mitogen. Whereas EGF inhibited the actions of IGF1 on aromatase activity, it did not inhibit the effects of IGF1 on the growth of granulosa cells. In summary, growth factors influence both the differentiation and growth of granulosa cells, and may be important regulators of follicular development.

Animals↗

PubMed1989

Comparison of insulin-like growth factor 1 and insulin effects on prolactin-induced lactogenesis in the rabbit mammary gland in vitro.

In organ culture of pregnant rabbit mammary gland, a low casein synthesis occurs with prolactin (PRL) alone. Insulin markedly potentiates the effect of PRL. Only pharmacological concentrations of insulin (5 micrograms/ml) exert the maximal enhancement, suggesting a possible interaction with the insulin-like growth factor 1 (IGF1) receptor. The presence of IGF1 and insulin binding sites was analyzed and the biological effects of both peptides were compared. Binding of iodinated human IGF1 or porcine insulin to mammary microsomes prepared from mid-pregnant rabbits revealed distinct high affinity binding sites for both peptides (Kd approximately 2 nM). In rabbit mammary explants, we confirmed that only non-physiological concentrations of insulin (greater than or equal to 100 ng/ml) exerted a significant stimulation of the PRL effect. Surprisingly, IGF1 was not found to be more potent than insulin on a molar basis, which did not provide evidence for the exclusive involvement of the IGF1 receptor. Near-physiological concentrations of IGF1 (approximately 100 ng/ml), however, exerted a significant enhancement which suggested a possible action for IGF1 on PRL-induced lactogenesis in vivo.

Animals↗

PubMed1990

Diffusion of insulin-like growth factor 1 in human breast cancer explants.

Tumor explants, from 15 patients with primary breast cancers, were incubated in organ culture medium containing [125I]IGF1. Measurements of explant radioactivity were performed in order to evaluate IGF1 uptake and release as a function of time, medium concentration and patient, in tumors with low IGF1 receptor levels. Uptake and release were governed by a passive diffusion mechanism and could be well described by a pharmacokinetic-like model. The rate of uptake depended on patient but affinity of IGF1 for the tumor tissue was always higher than affinity for the medium. Moreover the rate of uptake was faster than IGF1 clearance in man. From these results it can be extrapolated that the IGF1 circulating level must strongly influence the tumor content, independently of the receptor level. In the same way, IGF1 analogs could be administered via blood injection and the administration could be monitored by the above described pharmacokinetic model.

Breast Neoplasms↗

PubMed2003

Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas.

The insulin-like growth factor-1 receptor (IGF1-R) is a cellular receptor overexpressed in many tumor cell lines and in some human tumors that seems to play a critical role in transformation, tumorigenicity, and metastasis. To date, a comprehensive evaluation of tissue distribution of IGF1-R in human carcinomas from different anatomical sites has been lacking. Using stage-oriented human cancer tissue microarrays, we studied IGF1-R expression and distribution in a group of 152 human carcinomas from a variety of anatomical sites and from 63 normal tissues through immunohistochemistry. The tumors included carcinomas from breast (8), ovary (9), endometrium (7), esophagus (5), stomach (7), pancreas (7), liver (4), colon (10), kidney (14), bladder (17), prostate (11), head and neck (31), salivary glands (8), lung (13), and skin (1). Formalin-fixed, paraffin embedded tissues of each case were immuno-stained using the avidin-biotin peroxidase method and an anti-IGF1-R rabbit polyclonal antibody. High-membranous IGF1-R staining was observed in 7 of 8 (87.5%) breast carcinomas, in 9 of 9 (100%) ovarian carcinomas, in 7 of 7 (100%) endometrial carcinomas, in 5 of 7 (71.1%) gastric carcinomas, in 4 of 7 (57.1%) pancreatic carcinomas, in 9 of 10 (90%) colon adenocarcinomas, in 11 of 13 (84.6%) lung carcinomas, in 6 of 11 (54.5%) prostatic adenocarcinomas, and in 17 of 17 (100%) transitional cell carcinomas of the bladder. Only a minority of squamous cell carcinomas of the head and neck and esophagus (34), salivary gland tumors (5), and renal cell carcinomas (14) were IGF1-R positive. This study demonstrates the overexpression of IGF1-R across a wide variety of human carcinomas of glandular or transitional cell origin.

Adolescent↗

PubMed2001

Insulin-like growth factor I induced survival of axotomized olfactory neurons in the chick.

Insulin-like growth factor 1 (IGF1) receptor is expressed in avian olfactory neurons and IGF1 in the bulb. To explore the function of IGF1 in olfactory system in the chick, we infused IGF1 at the lesion site 0 and 12 h after olfactory axotomy. The animals were killed 1-3 days later. TdT mediated dUTP nick end labeling method and bromodeoxyuridine incorporation allowed the evaluation of programmed cell death and mitotic activity respectively in the olfactory epithelia of IGF1 treated or untreated lesioned animals and controls. IGF1 treatment suppressed the apoptotic wave, stimulated mitosis which peaked within 24 h (instead of 48 h), to return promptly to normal, and transiently maintained the number of calmodulin related kinase II expressing neurons at normal levels. It reveals a long lasting effect of IGF1 on the survival of lesioned olfactory neurons and transient effects on maintenance of differentiation and mitosis stimulation.

Animals↗

PubMed2006

The essential role of insulin-like growth factor-1 in the intestinal tropic effects of glucagon-like peptide-2 in mice.

BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that acts through unknown pathways to induce intestinal growth. We investigated the role of the insulin-like growth factors (IGF-1 and IGF-2) as mediators of GLP-2-enhanced growth in the murine intestine. METHODS: IGF-1 expression and secretion were determined in GLP-2-responsive primary intestinal cultures treated with GLP-2. Parameters of intestinal growth were assessed in wild-type (CD1, Igf1(+/+) and Igf2+), heterozygous (Igf1(+/-)), and null (Igf1(-/-) and Igf2(-P)) mice treated chronically with saline, GLP-2, IGF-1, or R-Spondin1. RESULTS: GLP-2 increased IGF-1 messenger RNA expression and IGF-1 secretion in intestinal cultures and increased expression of IGF-1 messenger RNA in mouse small intestine in vivo. Igf1(+/+) and Igf2+ mice responded to .1 microg/g(-1) per day(-1) GLP-2 with increased intestinal weights, morphometric parameters, and proliferative indices. In contrast, Igf1(-/-) mice were unresponsive to the same dose of GLP-2, failing to demonstrate changes in intestinal weight, morphometry, or proliferation. However, a significant effect of 1 microg/g(-1) per day(-1) GLP-2 was observed in Igf1(-/-) mice, but only in terms of small intestinal weight when normalized for body weight. Furthermore, Igf2(-P) mice demonstrated a partially impaired response in terms of small intestinal growth. Both Igf1(-/-) and Igf2(-P) mice exhibited normal-enhanced intestinal growth in response to IGF-1 and/or R-Spondin1. CONCLUSIONS: GLP-2 enhances intestinal IGF-1 expression and secretion, and IGF-1 is required for small and large intestinal growth in response to GLP-2. These findings identify IGF-1 as an essential mediator of the intestinotropic actions of GLP-2.

Animals↗

PubMed1999

Insulin-like growth factor 1 is required for G2 progression in the estradiol-induced mitotic cycle.

Insulin-like growth factor 1 (IGF1) has been proposed as a "G1-progression factor" and as a mediator of estradiol's (E2) mitogenic effects on the uterus. To test these hypotheses, we compared E2's mitogenic effects on the uteri of Igf1-targeted gene deletion (null) and wild-type littermate mice. The proportion of uterine cells involved in the cell cycle and G1- and S-phase kinetics were not significantly different in wild-type and Igf1-null mice. However, the appearance of E2-induced mitotic figures and cell number increases were profoundly retarded in Igf1-null uterine tissue. There was a significant increase in nuclear DNA concentration in Igf1-null cells, consistent with a G2 arrest. Interestingly, apoptotic cells were also significantly reduced in abundance, and the normal massive apoptotic response to E2 withdrawal was absent in the Igf1-null uterus. These data show that Igf1 is an essential mediator of E2's mitogenic effects, with a critical role not in G1 progression but in G2 progression.

Animals↗

PubMed2005

Insulin-like growth factor-I gene polymorphism associations with growth, body composition, skeleton integrity, and metabolic traits in chickens.

Molecular genetic selection on individual genes is a promising method to genetically improve economically important traits in chickens. A resource population was developed to study the genetics of growth, body composition, skeletal integrity, and metabolism traits. Broiler sires were crossed to dams of 2 diverse, highly inbred lines (Leghorn and Fayoumi), and the F1 birds were intermated by dam line to produce broiler-Leghorn and broiler-Fayoumi F2 offspring. Growth, body composition, skeletal integrity, and hormonal and metabolic factors were measured in 713 F2 individuals. Insulin-like growth factor-I (IGF1) was selected for study as a biological and positional candidate gene. A single nucleotide polymorphism (SNP) was identified between the founder lines in the IGF1 promoter region, and a PCR-RFLP assay was developed. A mixed model was used to statistically analyze associations of IGF1-SNP1 with phenotypic traits. The IGF1-SNP1 had significant associations with most recorded traits, except metabolic traits. Strong interactions between the IGF1 gene and genetic background on growth traits in the 2 F2 populations suggest that genetic interaction is an important aspect for consideration before using the IGF1-SNP1 in marker-assisted selection programs. Several beneficial effects (improved growth, increased breast muscle weight, decreased abdominal fat, and enhanced skeletal integrity) associated with 1 allele indicate the presence of 1 or more loci near IGF1-SNP1 controlling biologically diverse and economically important traits in chickens.

Animals↗

PubMed1992

The pro-region of the yeast prepro-alpha-factor is essential for membrane translocation of human insulin-like growth factor 1 in vivo.

Four yeast secretion signals, the 19-amino-acid invertase signal sequence, the 17-amino-acid acid-phosphatase signal sequence, and the pre-sequence and prepro-sequence of prepro-alpha-factor have been used to look for the secretion of recombinant human insulin-like growth factor 1 (IGF1) from Saccharomyces cerevisiae. Only the prepro-sequence, often referred to as the alpha-factor leader and consisting of an N-terminal 19-amino-acid pre-sequence or signal sequence attached to a 66-amino-acid pro-region, permits secretion of IGF1. The signal sequences alone do not allow the translocation of IGF1 into the endoplasmic reticulum. This is evident from the fact that IGF1-like molecules, to which the signal sequences are still attached, accumulate intracellularly in the cytosol. Fusion of the pro-region of the alpha-factor leader to the C-terminus of the acid-phosphatase and invertase signal sequences allows IGF1 to be secreted once again. These results reveal the essential role of the pro-region of the alpha-factor leader in the secretion of IGF1 and indicate that it may have a function in guiding a nascent IGF1 polypeptide to a state in which translocation can occur.

Amino Acid Sequence↗

PubMed1989

Insulin-like growth factor 1 as an intra-ovarian hormone--an integrated hypothesis and review.

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least 2 samples of clear follicular fluid (FF) collected in the late follicular phase. Dominant follicles contained significantly higher concentrations of insulin-like growth factor-1 (IGF1), oestradiol (E2), progesterone (P) and lower androstenedione (AD) than their matched cohorts. After the luteinizing hormone (LH) surge, a significant increase in dominant FF-IGF1 and FF-P occurred. Log FF-E2 and log FF-P were correlated with both FF-IGF1 and FF volume. Log FF-AD was negatively correlated with FF-volume, FF-E2 and FF-P (but not FF-IGF1). The cohort concentration of FF-IGF1 was correlated with serum IGF1. These results support the hypothesis that IGF1 has a central role in the selection of the dominant follicle.

Adult↗

PubMed1999

Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene.

Pituitary is influenced by circulating and locally produced insulin-like growth factor I (IGF-I). To further elucidate the role of pituitary IGF-I, we compared pituitary morphology of homozygous (IgfI-/-), heterozygous (IgfI+/+), and wild-type (IgfI+/+) fetal and adult mice using light microscopy, immunocytochemistry, in situ hybridization and electron microscopy. In pituitaries of Igf1-/- and Igf1+/- fetal mice (day 18.5) GH RNA signal was decreased. In Igf1-/- adult females, GH cells were significantly diminished in size; GH RNA signal was stronger in Igf1-/- mice compared with IgfI+/+ mice, and the somatotrophs had ultrastructural features of stimulation. The number of PRL cells and PRL hybridization signal were significantly decreased, however plasma PRL levels were elevated in both genders. No changes in other cell types in Igf1-/- mice, and no alterations in Igf1+/- mice were evident. IGF-I treatment for 2 weeks of Igf1-/- mice increased significantly body weights, decreased GH hybridization signal, and had no effect on PRL cells, or PRL plasma levels, whereas in IgfI+/+ mice, PRL RNA signal and PRL plasma levels were markedly increased. In conclusion, IGF-I plays no role in differentiation of pituitary cells, affects the size of somatotrophs in females, and is a stimulator of lactotrophs in both genders.

Aging↗

PubMed2005

[Effects of recombinant human growth hormone (GH) replacement therapy on bone metabolism in children with GH deficiency].

OBJECTIVE: To study the changes of bone turnover markers and bone mass in children with growth hormone (GH) deficiency before and after recombinant human GH replacement therapy. METHODS: Serum levels of bone turnover markers (OC, BAP and ICTP), IGF1 and distal radius bone mass (SOS SDS) of 37 cases with complete growth hormone deficiency (CGHD), 31 partial growth hormone deficiency (PGHD) and 31 age- and sex-matched healthy controls were measured. Twenty-nine patients received rhGH replacement therapy at dose of 0.03 mg/kg. day and the above parameters were measured every 3 or 6 months after treatment. RESULT: Compared with the control, baseline serum levels of BAP, ICTP and IGF1 in CGHD group were significantly decreased (P<0.05), so was IGF1 in PGHD group (P<0.05). Significantly positive correlation was found between IGF1 and ICTP (r=0.32, P=0.01) in CGHD group. There was no significant difference between GHD group and the control in other biochemical parameters. All bone turnover markers and IGF1 increased significantly in both CGHD and PGHD children after rhGH replacement therapy for 3 months (P<0.05). ICTP and IGF1 were increasing with the prolonged rhGH replacement therapy. A tendency of increase in distal radius SOS SDS was also seen after rhGH-treatment, though not statistically significant (P>0.05). CONCLUSION: Compared with the control, bone turnover markers BAP and ICTP are lower in children with CGHD, with lower IGF1 but unchanged bone mass in both CGHD and PGHD. All bone turnover markers can be significantly improved in GHD children after rhGH replacement treatment for 6 months, with a tendency of increase in bone mass.

Alkaline Phosphatase↗

PubMed2003

Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway.

Colon cancer overexpresses insulin-like growth factor 1 (IGF1) and insulin-like growth factor 1 receptor (IGF1-R), as compared with normal or adenomatous mucosa, and it has been postulated that colorectal cancer cells depend on the IGF1/IGF1-R pathway for their growth and progression. In this study, using the human colon cancer cell line HCT116, we find that established HCT116/IGF1-R transfectants exhibit a more aggressive transformed phenotype than the parental cell line, as demonstrated by their higher proliferation rate in response to IGF1, higher degree of anchorage-independent growth, resistance to serum deprivation-induced apoptosis, and higher migratory capability in a monolayer "wounding assay." When injected into nude mice, HCT116/IGF1-R transfectants were highly invasive and produced distant metastases, whereas the parental cell did not. Moreover, the overexpression of IGF1-R in these cells was associated with IGF1-R-induced activation of Akt and up-regulation of the antiapoptotic protein Bcl-x(L). We also show that Akt pathway mediates IGF1-R-induced Bcl-x(L) expression at transcriptional level. Our data demonstrate, for the first time, that IGF1-R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype, in a subset of colorectal cancers.

Animals↗

PubMed2006

A theoretical study of the distribution of insulin-like growth factor in human articular cartilage.

We present a mathematical simulation which integrates the mechanisms that are currently believed to govern the concentration of the growth factor, IGF1, in cartilage. Articular cartilage is treated as a two-layer continuum: a thin surface layer, exposed to synovial fluid, with a higher cell density, and a deeper layer with impermeable bony endplate. A system of differential equations accounts for diffusion of IGF1 from synovial fluid into, and throughout, the cartilage; IGF1 synthesis, its reactions with soluble binding protein, with cell receptors, and with immobile binding sites on the extracellular matrix. We have collected all available physiologic data relevant to the solution of these equations and used it to compute numerical solutions that yield time dependent profiles for free and complex IGF1 throughout the depth of normal cartilage. Equations for osteoarthritic cartilage were formulated as well. Numerical results indicate a time-scale of several days for IGF1 profiles to settle down after a disturbance. The number of cell receptors for IGF1 appears to be more important than their rate of internalization. There is a lower bound to the number of cell receptors and of immobile binding sites. Parameters that await experimental determination are identified.

Carrier Proteins↗

PubMed1998

Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure.

BACKGROUND: Congestive heart failure (CHF) is characterized by increased activity of the renin-angiotensin system. Recent experimental studies have shown that infusion of angiotensin II results in depressed plasma levels of insulin-like growth factor 1 (IGF-1) and weight loss. We have previously reported that stable patients with CHF have decreased activity of the growth hormone (GH)-IGF1 axis. We have hypothesized, therefore, that angiotensin-converting enzyme (ACE) inhibition therapy should restore GH-IGF1 activity in CHF patients. METHODS AND RESULTS: Nine patients with stable CHF who were taking digitalis and diuretics, New York Heart Association functional class III were studied before and after 8 weeks of therapy with Enalapril (10 mg twice daily). We measured IGF1 levels, radionuclide left ventricular ejection fraction (EF) and peak oxygen consumption (PVO2). We found that 7 of 9 patients had abnormally low levels of IGF1 (0.2-0.5 mU/ml). IGF1 levels reverted to normal after Enalapril therapy (0.36 +/- 0.03 to 0.8 +/- 0.14 mU/ml, P = .004). This was associated with a significant increase in EF (27.4 +/- 1.1 to 31.4 +/- 0.9%) and PVO2 (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min) values (P < .05). CONCLUSION: Chronic ACE inhibition therapy restored previously reduced IGF1 plasma levels in patients with CHF, most likely by reducing angiotensin II activity.

Adult↗

PubMed2003

Modification of insulin-like growth factor 1 receptor, c-Src, and Bcl-XL protein expression during the progression of Barrett's neoplasia.

Oncogenes, growth factors, cell surface receptors, and cell-cycle and apoptotic regulatory proteins have been implicated in the growth regulation and progression of Barrett's-associated neoplasia. Among these, insulin-like growth factor 1 receptor (IGF1-R) and c-Src are reported to be key regulators of mitogenesis and tumorigenesis. In addition, c-Src may exert its transforming capability by inducing increased expression of IGF1-R on the neoplastic cells. Bcl-X(L), a member of the Bcl-2 family, blocks apoptosis and has been reported to increase in Barrett's-associated neoplasia. To study the modifications in IGF1-R, c-Src, and Bcl-X(L) protein expression during the progression of Barrett's-associated neoplasia, we analyzed 34 resected gastroesophagectomy specimens by immunohistochemistry using antibodies to human IGF1-R, c-Src, and Bcl-X(L). In these cases, we found 22 intestinal (Barrett's) metaplasias (IMs), 25 low-grade dysplasias (LGDs), 28 high-grade dysplasias (HGDs), 34 invasive adenocarcinomas (CAs), and 19 lymph node metastases. High IGF1-R cytoplasmic staining was present in 14 of 19 (74%) node metastases, in 28 of 34 (82%) CAs, in 18 of 28 (64%) HGDs, in 13 of 25 (52%) LGDs, and in 5 of 22 (23%) IMs. Strong and diffuse c-Src expression was identified in 17 of 19 (89%) node metastases, in 29 of 34 (85%) Cas, in 26 of 28 (93%) HGDs, in 18 of 25 (72%) LGDs, and in 9 of 22 (41%) IMs. Bcl-X(L) cytoplasmic staining was evident in 12 of 19 (63%) node metastases, in 20 of 34 (59%) Cas, in 20 of 28 (71%) HGDs, in 15 of 25 (60%) LGDs, and in 6 of 22 (27%) IMs. In 11 cases, c-Src activity was measured by kinase assay and reflected the immunohistochemical results. Our data indicate that expression levels of IGF1-R, c-Src, and Bcl-X(L) proteins are coordinately elevated in Barrett's-associated neoplasia. These findings indicate important roles of these growth regulatory proteins in the malignant progression of Barrett's-associated neoplasia.

Adenocarcinoma↗