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Biomedical subjects

M Kan

Publications and source records attributed to M Kan.

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

Fibroblast growth factor receptor 2 limits and receptor 1 accelerates tumorigenicity of prostate epithelial cells.

Progressive loss of the differentiated phenotype and communication with stroma accompanies the transition of nonmalignant rat prostate epithelial cells to anaplastic, malignant tumors. Here we show that cell surface expression of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase is reduced in malignant tumor cell populations (type II) and undetectable at the mRNA level in 30% of cells. This is in addition to the irreversible loss by splice switching of the FGFR2 ectodomain that abrogates response to FGF-7 and homologues from the stroma. One hundred % of type II malignant cells express FGFR1, which is normally expressed in the stroma. Expression of the FGFR1 kinase in premalignant type I tumor epithelial cells by transfection accelerated progression to the malignant phenotype. In contrast to the FGFR2 kinase fused to the ectodomain of FGFR1, the FGFR1 kinase failed initially to support a mitogenic response to FGF-2 in type I tumor cells. However, the FGFR1-transfected cells acquired a mitogenic response after extensive proliferation of the cell population. Resident FGFR2 and ectopic FGFR1 appeared to be partitioned in the type I cells, because neither full-length nor truncated isoforms of FGFR1 affected the mitogenic response of the other. Restoration of the FGFR2IIIb kinase to malignant cells expressing FGFR1 depressed tumor growth rates, restored responsiveness to stromal cells, and restored epithelial cell differentiation. These observations reveal that homologous FGFR1 and FGFR2 kinases play very different roles in cell growth and differentiation and in development and support of the malignant phenotype.

Animals↗
PubMed1997

A homeo-interaction sequence in the ectodomain of the fibroblast growth factor receptor.

Interaction of fibroblast growth factor receptors (FGFR) sufficient for a trans-phosphorylation event in which one intracellular domain is substrate for the other is essential for signal transduction. By analysis of the direct interaction of recombinant constructions co-expressed in baculoviral-infected insect cells, we identified a 17-amino acid sequence that is required for the stable interaction between ectodomains of FGFR. The sequence 160ERSPHRPILQAGLPANK176 (Glu160-Lys176) connects immunoglobulin modules II and III. In insect cells, the interaction between Glu160-Lys176 domains occurs independently of intact heparin or FGF binding domains. The sequence is not required for the binding of heparin or FGF-1, but is essential for mitogenic activity of the FGFR kinase in mammalian cells. The results support a model in which the homeo-interaction between Glu160-Lys176 in the ectodomain contributes to the interaction between intracellular domains in mammalian cell membranes (Kan, M., Wang, F., Kan, M., To, B., Gabriel, J. L., and McKeehan, W. L. (1996) J. Biol. Chem. 271, 26143-26148). We propose that the Glu160-Lys176 domain plays a pivotal role in restriction of the interaction between kinases by pericellular matrix heparan sulfate proteoglycan and divalent cations. Restrictions are overcome by FGF or constitutively by diverse gain of function mutations which cause skeletal and craniofacial abnormalities.

Amino Acid Sequence↗
PubMed1997

Growth and differentiation of periodontal ligament-derived cells in serum-free defined culture.

We have developed a serum-free medium for the growth and differentiation of periodontal ligament-derived cells (PLC). In addition, the expression of both fibroblast growth factor (FGF) and FGF receptor (FGFR) in the PLC was investigated by immunohistochemical examination, heparin affinity chromatography (HAC), and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Optimal growth of the cells was achieved in Iscove's modified Dulbecco's medium supplemented with insulin, transferrin, 2-mercaptoethanol, 2-ethanolamine, sodium selenite, and oleic acid in type-I collagen-coated dishes. Both FGF-1 and FGF-2 stimulated cell growth and inhibited differentiation as measured by inhibition of alkaline phosphatase activity of the cells. An immunohistochemical analysis of FGF-1 and FGF-2 revealed that immunoreactive FGF-1 and FGF-2 were detected predominantly in the cytoplasm of growing cells. In addition, perinuclear FGF-1 staining and nuclear FGF-2 staining were observed in the same growing cells. In contrast, a faint diffuse staining of FGF-1 and FGF-2 was detected in cytoplasm of the confluent differentiated cells. The 2.15 M NaCl eluate from HAC of the cell extracts exhibited growth-promoting activities for the PLC, and it also stimulated the growth of human umbilical vein-derived endothelial cells and inhibited binding of [125I]-FGF to its receptors, indicating the cells produced FGFs or FGF-like growth factors. RT-PCR analysis revealed that the cells expressed FGFR-1 mRNA but not mRNAs for FGFR-2, FGFR-3 and FGFR-4 mRNA. These results suggest that the FGF-FGFR-1 system plays an important role in the growth and differentiation of periodontal ligament-derived cells.

Alkaline Phosphatase↗
PubMed1997

Immunohistochemical localization of fibroblast growth factor-1 (FGF-1), FGF-2 and fibroblast growth factor receptor-1 (FGFR-1) in pleomorphic adenoma of the salivary glands.

Fibroblast growth factor-1 (FGF-1) and FGF-2 are heparin-binding polypeptides that are potent mitogens for neoplastic cells. In this study, fibroblast growth factor-1 (FGF-1), FGF-2, and fibroblast growth factor receptor-1 (FGFR-1) were immunohistochemically analyzed in 10 patients with pleomorphic adenoma of the salivary gland by using specific monoclonal antibodies. The tumor tissues were histopathologically classified as: tubular, solid, myxoid or chondroid. Both FGF-1 and FGF-2 were immunohistochemically identified in the tumor cells of all histological types. In addition, immunoreactive FGF-2 was also found in the basement membrane of tubular type tumor cells. Conversely, FGFR-1-positive tumor cells were essentially confined to the tubular and solid areas of tumors. Tumor cells in the myxoid and chondroid areas were FGFR-1 immunonegative. These results suggest that the co-expression of FGF and its receptor appears to be related to the proliferative activity of tumor cells in the tubular and solid areas, whereas loss of FGF receptor expression may be associated with the differentiation of tumor cells into myxoid and chondroid tissue types.

Adenoma, Pleomorphic↗
PubMed1997

Heparin-dependent fibroblast growth factor activities: effects of defined heparin oligosaccharides.

Heparin and related molecules have been identified as important participants in fibroblast growth factor (FGF) signaling although the mechanisms of action remain unclear. We have used heparin oligosaccharides to examine steps in the signaling process which could be affected by the polysaccharide. Immobilized FGF-1 and FGF-2 bound all sizes of oligosaccharides tested, ranging from tetrasaccharide to decasaccharide, at physiological salt concentration. Each group of oligosaccharide was eluted from the FGF affinity columns in several peaks, and larger oligosaccharides showed higher apparent affinity for the immobilized growth factors compared to the shorter ones. Heparin hexasaccharides were the smallest fragments providing complete protection of FGF-1 and FGF-2 against trypsin digestion. Tetrasaccharides, however, were able to provide partial protection. The requirement of heparin for ligand-receptor interaction was evaluated in receptor binding assays using Sf9 insect cells engineered to overexpress different recombinant FGF receptor (FGFR) species including FGFR1 beta, FGFR1 alpha or FGFR4 at the cell surface. In these assays hexasaccharides were the smallest fragments capable of stimulating FGF-receptor interaction. Over the range of concentrations examined, neither hexasaccharides nor octasaccharides were able to stimulate receptor binding to the level attained by intact heparin. In fact, these oligosaccharides interfered with the ability of intact heparin in promoting FGF-receptor binding. The presence of both stimulatory and inhibitory activities in hexasaccharide and octasaccharide populations could be attributed to structural heterogeneity within the oligosaccharide preparations. However, similar observations were obtained with "highly-sulfated" structurally homogeneous preparations of hexasaccharide and octasaccharide, although these molecules generally had greater stimulatory and less inhibitory activity than their structurally heterogeneous counterparts. Hexasaccharides were found to be the smallest fragments able to potentiate the FGF-1-induced 3T3 cell proliferation while their effect on FGF-2 signaling was less clear. These observations suggest that heparin can modulate FGF-signaling at several stages with different end results.

3T3 Cells↗
PubMed1997

Skin dose reduction by a clinically viable magnetic deflector.

A variable magnetic deflector which attaches onto the treatment head of a linear accelerator has reduced skin dose by as much as 65% for 6MV x-rays. The magnetic deflector is constructed from Neodymium Iron Boron (NdFeB) rare earth magnets. It weighs approximately 15 kg and is designed to easily fit onto the accessory mount of a clinical linear accelerator. All field sizes are attainable up to 35 cm x 35 cm at 100 cm SSD. The gap between the magnetic poles can be adjusted, providing the highest field strength for each field size. Magnetic field strengths up to 0.55 Tesla are attainable. For a 6MV x-ray beam with a 10 mm perspex block tray, surface dose is reduced from 29% to 14% and from 59% to 37% for a 20 cm x 20 cm and 35 cm x 35 cm field size, respectively. Results at varying SSD's have shown at least 10 cm of space must be allowed between the magnets and patient for adequate reduction of skin dose through removal of electron contaminants.

Humans↗
PubMed1997

[Management of subarachnoid hemorrhages without detectable aneurysm].

In this study, 21 patients with subarachnoid hemorrhage (SAH) but negative angiography were evaluated. Angiography was performed twice on each patient, that is, on admission and at 2 weeks following admission. All patients had severe headache of sudden onset, a characteristic manifestation of SAH. Clinical grades on admission (Hunt and Kosnik classification) were generally good: 17 patients were in grade I or II and 4 patients were in grade III. SAH was confirmed by the presence of subarachnoid clot on CT in all cases. Based on the distribution of SAH, CT findings were classified into two patterns, i.e., perimesencephalic and non-perimesencephalic patterns. Four patients showed the perimesencephalic pattern and the remaining 17 the non-perimesencephalic. The period of follow-up ranged from 20 days to 11 years 6 months, with a mean of 6 years 10 months. Except for three recent cases, the mean follow-up period in 8 years 9 months. Exploratory craniotomies probing for aneurysms have been performed in four patients, but no aneurysms have been found in any of these cases. Clinical deterioration associated with vasospasm was observed in one patient. A communicating hydrocephalus requiring a shunting procedure was observed in three patients showing the non-perimesencephalic type CT pattern. Rebleeding occurred in one patient who subsequently died of what may be a dissecting aneurysm of the vertebral artery. One patient who was able to return to full activity experienced symptoms attributable to SAH such as frequent headaches and increased fatigability. Complete recovery was observed in the remaining 19 patients. Two of them, however, later died due to myocardial infarction and aging, respectively. Given these generally positive outcomes, it should be possible to inform such patients of the benignity of their condition. Angiography may not demonstrate a ruptured aneurysm on initial examination in all cases of aneurysmal SAH. Serial angiography, however, can provide a definite diagnosis of the dissecting aneurysm. Therefore, repeat angiography, particularly, when possible, digital subtraction angiography, is necessary to rule out aneurysmal SAH. While small aneurysms or microaneurysms are often found through exploratory craniotomy, we do not agree with the opinion that surgery may be appropriate for certain patients with SAH but with negative angiography. The natural history concerning rebleeding in such cases, as well as morbidity and mortality associated with hemorrhage, remains to be defined. Furthermore, there are reservations regarding whether coagulation of these abnormalities with bipolar cautery constitutes definitive treatment.

Adult↗
PubMed1997

Direct extracranial-intracranial bypass for children with moyamoya disease.

To improve cerebral hypoperfusion in the ischemic type of Moyamoya disease, we have applied superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses in combination with encephalo-myo-synangiosis (EMS) for 19 hemispheres of 10 children (age from 5 to 11 years at surgery). Two branches of the STA were anastomosed to the two cortical arteries which were selected in the watershed area of the cerebral hemisphere estimated as a hypoperfusion area on the preoperative angiograms. Before surgery transient ischemic attacks (TIAs) developed from every month to every 6 months in association with hyperventilation or sobbing. No perioperative completed stroke or wound complications was observed, although single TIA developed in four patients within 1 month after surgery. Postoperative angiogram demonstrated that, not only the preoperative watershed area, but also the most of the middle cerebral artery territory was oppacified via the 2 branches of the STA in all 19 hemispheres. In a mean follow-up period of 4 years, no ischemic episode was induced by hyperventilation, and there was no mental or neurological deterioration. STA-MCA double anastomoses, to the cerebral watershed area, in combination with EMS are safe and effective even for younger children with Moyamoya disease.

Anastomosis, Surgical↗
PubMed1996

Molecular modeling and deletion mutagenesis implicate the nuclear translocation sequence in structural integrity of fibroblast growth factor-1.

The sequence NYKKPKL in the NH2 terminus of fibroblast growth factor (FGF)-1 has been proposed to affect the long term activities of FGF-1 through its function as a nuclear translocation signal or its role in stabilization of the structure required to sustain binding and activation of the transmembrane receptor kinase. A dynamic molecular model of FGF-1 docked into a duplex of the FGF receptor ectodomain and a hexadecameric heparin chain suggests that the NYKKPKL sequence does not directly interact with heparin or the receptor, but rather the lysine-leucine residues within the sequence indirectly stabilize a major receptor-binding domain. Concurrent with a marked increase in dependence on exogenous heparin for optimal activity, sequential deletion of residues in the NYKKPKL sequence in FGF-1 resulted in a progressive loss of thermal stability, resistance to protease, mitogenic activity, and affinity for the transmembrane receptor. The largest change resulted from deletion of the entire sequence through the lysine-leucine residues. In the presence of sufficiently high concentrations of heparin, the deletion mutants exhibited mitogenic activity equal to wild-type FGF-1. The results confirm that a primary role of the NYKKPKL sequence domain is to maintain the structural integrity of FGF-1 required for optimal binding to and activation of the heparan sulfate-transmembrane receptor complex.

3T3 Cells↗
PubMed1996

Divalent cations and heparin/heparan sulfate cooperate to control assembly and activity of the fibroblast growth factor receptor complex.

Polypeptides of the fibroblast growth factor (FGF) family are ubiquitous bioregulators within tissues whose activity is controlled by heparan sulfates within the pericellular matrix. FGF and the ectodomain of their transmembrane tyrosine kinase receptors (FGFR) exhibit heparin-binding domains that when juxtaposed in a FGF middle dotFGFR complex can accommodate a single, potentially bivalent, decameric polysaccharide chain in a ternary complex. Here we show that the interaction of heparin with FGF ligands is not affected by divalent cations. In contrast, the high affinity interaction (apparent Kd = 10 nM) of heparin with FGFR requires Ca2+ or Mg2+ at physiological concentrations. Divalent cations maintain FGFR in a heparan sulfate-dependent state in respect to FGF binding and an FGF- and heparan sulfate-dependent state in respect to autophosphorylation. A model is proposed where divalent cations and heparan sulfate cooperate to maintain FGFR in a conformation that restricts trans-phosphorylation between intracellular kinase domains. The restriction is overcome by FGF or constitutively as a common consequence of diverse mutations in FGFR associated with skeletal and craniofacial abnormalities.

Binding Sites↗
PubMed1996

Androgen-dependent expression of fibroblast growth factor-1 in submaxillary gland of mouse.

We have purified a 16,000 dalton protein that stimulates growth of human umbilical cord vein-derived endothelial cells (HUV-EC) from mouse submaxillary glands by using heparin-Sepharose affinity and C4 reverse phase chromatography. The purified molecule was identified as an FGF-1 on the basis of its biological activities, its affinity for heparin and its N-terminal amino-acid sequence. The concentrations of FGF-1 in the submaxillary gland of male or testosterone-treated female mice were about 12 times those of untreated females or castrated males. The 2.3 and 4.1 kb FGF-1 mRNAs were expressed in the glands of male mice older than 4 weeks but not in the glands of female mice. These results suggest that FGF-1 may have important functions for growth, differentiation and development of mouse submaxillary glands, and it may act as an endocrine hormone.

Amino Acid Sequence↗
PubMed1996

Expression of fibroblast growth factor-1 (FGF-1), FGF-2 and FGF receptor-1 in a human salivary-gland adenocarcinoma cell line: evidence of growth.

Fibroblast growth factor-1 (FGF-1) and FGF-2 are heparin-binding polype ptides which express potent mitogenic properties in neoplastic cells. In the present study, we have examined the contribution of endogenous FGF-1 and FGF-2 to the autocrine growth of HSY human salivary-gland adenocarcinoma cells in vitro. Using specific monoclonal antibodies against FGF-1 and FGF-2, immunohistochemical analysis of HSY cells revealed strong expression of both FGF-1 and FGF-2 in the cytoplasm and nucleus. Consistent with these data, 2 molecular mass species of FGF-1 (16 and 18 kDa) and 3 FGF-2 (18, 24 and 27 kDa) were identified in HSY cells by Western-blot analysis. Scatchard analysis of FGF binding sites on HSY cells indicated the presence of 23,000 [125I]FGF-1 binding sites/cells with a dissociation constant (KD) of 178 pM and 13,000 [125I]FGF-2 binding sites/cell with a KD of 102 pM. In addition, HSY cells were shown to express the mRNA for FGF receptor-1 (FGFR-1) by reverse transcription-polymerase chain reaction (RT-PCR), confirming the existence of high-affinity FGF binding sites. The influence of endogenous FGF-1 and FGF-2 on HSY cell growth was evaluated by suppressing the expression and activity of FGF by using anti-sense oligonucleotides and neutralizing antibodies. The addition of 50 micron FGF-1-specific anti-sense oligonucleotides to HSY cells resulted in a 61% inhibition of cell growth, while 50 microM FGF-2-specific anti-sense oligonucleotides resulted in a 76% inhibition. These effects were dose-dependent and specific, since sense oligonucleotides were ineffective in inhibiting HSY cell growth at the same concentration. Furthermore, HSY cell growth was suppressed in the presence of anti-FGF-1 or anti-FGF-2 neutralizing antibody, resulting in a 58% inhibition at 8 micromilligrams/ml. Our observations suggest that FGF-1 and FGF-2 may act as autocrine regulators by interacting with FGF receptors on HSY cells.

Adenocarcinoma↗
PubMed1996

Nuclear localization of a complex of fibroblast growth factor(FGF)-1 and an NH2-terminal fragment of FGF receptor isoforms R4 and R1alpha in human liver cells.

FGF ligands and FGF receptor 1 (FGFR1) appear associated with the nucleus in addition to their extracellular and transmembrane locations. After receptor-dependent internalization in liver cells, radiolabeled 16-kDa FGF-1 appears in a 40-kDa covalent complex with a cellular protein. In this report, we show that in a human hepatoma cell line, HepG2, which expresses both FGFR4 and FGFR1, the 40-kDa complex cross-reacts with antibodies against the ectodomain of both types of receptors. In addition to antibody against FGF-1, a polyclonal antiserum against the three immunoglobulin (Ig)-like loop ectodomain of FGFR4 and a monoclonal antibody to a 19-residue sequence in the NH2-terminus of the NH2-terminal Ig Loop I of the three loop splice variant of FGFR1 (FGFR1alpha) reacts with the complex. A monoclonal antibody against an epitope in FGFR1 downstream of the inter-loop I/II sequence which reacts with intact FGFR1 failed to cross-react with the 40-kDa complex. Cell fractionations and indirect immunofluorescent localization revealed that the 40-kDa complex associates with the particulate fraction of cells, particularly the nucleus and associated cytoskeletal elements. We propose that the NH2-terminal Ig-loop of the three loop isoforms of FGFR, which are generally associated inversely with cell growth, may play a role at or in the nucleus in addition to modification of affinity of the FGFR ectodomain for heparan sulfate and FGF ligand.

Antibodies↗
PubMed1996

Immunohistochemical study of overexpression of fibroblast growth factor-1 (FGF-1), FGF-2, and FGF receptor-1 in human malignant salivary gland tumours.

Fibroblast growth factor-1 (FGF-1) and FGF-2 are broad spectrum mitogens. The expression of FGF-1, FGF-2, and their receptor, FGF receptor-1 (FGFR-1), was examined in malignant salivary gland tumours and normal salivary glands, using immunohistochemical methods. In seven cases of adenoid cystic carcinoma (ACC), both duct-like cells and modified myoepithelial cells were apparently immunopositive for FGF-1, FGF-2, and FGFR-1. In five cases of mucoepidermoid carcinoma (MC), all three types of tumour cells including epidermoid cells, and intermediate cells expressed immunoreactive FGF-1, FGF-2, and FGFR-1. In these malignant salivary gland tumours, increased expression of FGFR-1 correlated with the intensity of both FGF-1 and FGF-2 immunoreactivity. In contrast to malignant salivary gland tumours, eight cases of normal salivary gland showed negative immunostaining for FGF-1, FGF-2, and FGFR-1 while four cases were weakly immunoreactive for FGF and its receptor. These results demonstrate that malignant salivary gland tumours overexpress FGF-1, FGF-2, and FGFR-1 compared with normal salivary glands and suggest that these growth factors may play an important role in facilitating neoplastic progression in human salivary glands.

Adult↗
PubMed1996

Reconstitution of a pentameric complex of dimeric transforming growth factor beta ligand and a type I, II, III receptor in baculoviral-infected insect cells.

Two transmembrane serine-threonine kinases (type I and II receptors), a membrane-anchored proteoglycan (type III), and a homodimeric ligand participate in the transforming growth factor beta type one (TGF beta 1) signal transduction complex. The expression of recombinant receptors in insect cells co-infected with up to three recombinant baculoviruses was employed to study interactions among the ectodomains of the three types of receptors and the TGF beta 1 ligand in absence of uncontrollable extrinsic factors in mammalian cells. Multi-subunit complexes were assembled in intact cells and purified on glutathione-conjugated beads for analysis by tagging one of the subunits with glutathione S-transferase (GST). Intrinsic ligand-independent interactions were observed among receptor subunits as follows: type III-III, type I-I, type III-I, and type II-I. The homeotypic complex of type II-II receptors and the heterotypic type III-II interaction was ligand dependent. The type I, but not the type III, subunit displaced about 50% of the type II component in either ligand-dependent homomeric type II-type II complexes or heteromeric type III-type II complexes to form type II-I or type III-II-I oligomers, respectively. The type II subunit displaced type I subunits in oligomers of the type I subunit. Specificity of type I receptors may result from differential affinity for the type II receptor rather than specificity for ligand. A monomeric subunit of the TGF beta 1 ligand bound concurrently to type III and type II or type III and type I receptors, but failed to concurrently bind to the type II and type I subunits. The binding of TGF beta 1 to the type I kinase subunit appears to require an intact disulfide-linked ligand dimer in the absence of a type III subunit. The combined results suggest a pentameric TGF beta signal transduction complex in which one unit each of the type III, type II, and type I components is assembled around the two subunits of the dimeric TGF beta ligand. An immobilized GST-tagged subunit of the receptor complex was utilized to assemble multi-subunit complexes in vitro and to study the phosphorylation events among subunits in the absence of extrinsic cell-derived kinases. The results revealed that (a) a low level of ligand-independent autophosphorylation occurs in the type I kinase; (b) a high level of autophosphorylation occurs in the type II kinase; (c) both the type III and type I subunits are trans-phosphorylated by the type II subunit; and (d) the presence of both type I and II kinases complexed with the type III subunit and dimeric TGF beta 1 ligand in a pentameric complex causes maximum phosphorylation of all three receptor subunits.

Animals↗
PubMed1996

Serological evaluation of soluble CD44 in renal cancer.

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme-linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico-pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745+/-170 ng/ml vs. 563+/-159 ng/ml, P=0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287+/-121 vs. 220+/-59, P=0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico-pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth-type cancers than in the slow growth-type cancers (3.95+/-2.12 vs. 2.63+/-0.82, P = 0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth-type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth-type cancers.

Adolescent↗
PubMed1996

Induction of FGF-7 after kidney damage: a possible paracrine mechanism for tubule repair.

A member of the fibroblast growth factor (FGF) family, keratinocyte growth factor (FGF-7 has unique specificity for epithelial cells. We investigated the role of FGF-7 in repair of proximal tubular damage caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). In situ hybridization localized FGF-7 to interstitial cells in the medulla and outer stripe of the outer medulla. Interstitial FGF-7 expression increased throughout the kidney 1 day after TFEC treatment. FGFR2 IIIb mRNA was high in the papilla and medulla and also increased after TFEC administration. By in situ hybridization, FGFR2 IIIb was localized to the tubular epithelium, particularly in collecting ducts. Proliferation of collecting duct epithelial cells increased in adult kidney after damage to the proximal tubule. FGFR2 IIIb, but not FGF-7, mRNA was also expressed by rat proximal tubule epithelial (RPTE) cells in vitro, and FGF-7 increased DNA synthesis in RPTE. Thus FGFR2 IIIb and FGF-7 expression is segregated between epithelial and interstitial cells forming a paracrine growth factor loop. These results raise the possibility that a novel paracrine growth loop is activated by chemical damage and regulates epithelial cell growth during tubular repair.

Aging↗