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At least 19 recordsLinked to original sources

PubMed1989

Sequence-specific 1H-NMR assignments and identification of two small antiparallel beta-sheets in the solution structure of recombinant human transforming growth factor alpha.

Transforming growth factor alpha (TGF alpha) is a small mitogenic protein with about 35% sequence identity with epidermal growth factor (EGF). TGF alpha-like proteins have been proposed to play a role in oncogenesis and wound healing. This report describes sequence-specific 1H-NMR resonance assignments for recombinant human TGF alpha (hTGF alpha). These assignments provide the basis for interpreting NMR data which demonstrate that the solution structure of hTGF alpha includes an antiparallel beta-sheet involving residues Gly-19 to Leu-24 and Lys-29 to Cys-34 and a second, smaller, antiparallel beta-sheet involving residues Tyr-38 and Val-39 and His-45 and Ala-46. These data, together with constraints imposed by the disulfide bonds, are combined to construct a molecular model of the polypeptide chain fold for residues Cys-8 to Ala-46. The resulting structure is similar to that of mouse and human EGF. Human TGF alpha and mouse EGF, however, differ with respect to their structural dynamics, since amide proton/deuteron exchange is much faster for hTGF alpha than for mouse EGF at pH 3.5.

Escherichia coli↗

PubMed1988

Structure-function analysis of synthetic and recombinant derivatives of transforming growth factor alpha.

Transforming growth factor alpha (TGF-alpha) is a 50-amino-acid peptide that stimulates cell proliferation via binding to cell surface receptors. To identify the structural features of TGF-alpha that govern receptor-ligand interactions, we prepared synthetic peptide fragments and recombinant mutant proteins of TGF-alpha. These TGF-alpha derivatives were tested in receptor binding and mitogenesis assays. Synthetic peptides representing the N terminus, the C terminus, or the individual disulfide constrained rings of TGF-alpha did not exhibit receptor-binding or mitogenic activity. Replacement of the cysteines with alanines at positions 8 and 21, 16 and 32, and 34 and 43 or at positions 8 and 21 and 34 and 43 yielded inactive mutant proteins. However, mutant proteins containing substitutions or deletions in the N-terminal region retained significant biologic activity. Conservative amino acid changes at residue 29 or 38 or both and a nonconservative amino acid change at residue 12 had little effect on binding or mitogenesis. However, nonconservative amino acid changes at residues 15, 38, and 47 produced dramatic decreases in receptor binding (23- to 71-fold) and mitogenic activity (38- to 125-fold). These studies indicate that at least three distinct regions of TGF-alpha contribute to biologic activity.

Amino Acid Sequence↗

PubMed1990

Human eosinophils express transforming growth factor alpha.

Transforming growth factor alpha (TGF-alpha) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-alpha (hTGF-alpha). No other identifiable leukocytes in these lesions contained detectable hTGF-alpha mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-alpha mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-alpha peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-alpha was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-alpha mRNA and none of these eosinophils contained immunohistochemically detectable TGF-alpha product. Taken together, these findings establish that human eosinophils can express TGF-alpha, but suggest that the expression of TGF-alpha by eosinophils may be under microenvironmental regulation. Demonstration of TGF-alpha production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.

Adenocarcinoma↗

PubMed1989

Regulation of transforming growth factor alpha and transforming growth factor beta messenger ribonucleic acid abundance in T-47D, human breast cancer cells.

Both transforming growth factor beta (TGF beta) and TGF alpha mRNA are expressed in human breast cancer cell lines. We have investigated the relationship of mRNA abundance for these growth modulators to the proliferation rate of a number of human breast cancer cell lines. Furthermore, we have investigated the relationship of regulation of TGF beta and TGF alpha mRNA to growth inhibition caused by progestins and nonsteroidal antiestrogens in T-47D human breast cancer cells. The abundance of TGF beta and TGF alpha mRNA in human breast cancer cell lines was not related directly to proliferation rate of the cells in culture or estrogen receptor positivity or negativity. The relationship of TGF beta and TGF alpha mRNA to growth inhibition caused by antiestrogens and progestins was investigated in T-47D human breast cancer cells. We observed that in T-47D human breast cancer cells the abundance of TGF beta mRNA is decreased in a time- and dose-dependent fashion by progestins but remains unaltered by nonsteroidal antiestrogens. Treatment of T-47D cells for 24 h with 10 nM medroxyprogesterone acetate (MPA) reduced the level of TGF beta mRNA to one third that present in untreated cells. The same treatment increased TGF alpha mRNA 3-fold above untreated controls in a time- and dose-dependent fashion and nonsteroidal antiestrogens caused a small decrease. The regulation of both TGF alpha and TGF beta mRNA was not directly related to inhibition of growth by progestins and antiestrogens in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

PubMed1990

8-Chloro-cAMP inhibits transforming growth factor alpha transformation of mammary epithelial cells by restoration of the normal mRNA patterns for cAMP-dependent protein kinase regulatory subunit isoforms which show disruption upon transformation.

Differential regulation of the regulatory subunits of cAMP-dependent protein kinase isozymes correlates with the growth inhibitory effect of site-selective 8-Cl-cAMP demonstrated in cancer cell lines (Ally, S., Tortora, G., Clair, T., Grieco, D., Merlo, G., Katsaros, D., Ogreid, D., Døskeland, S.O., Jahnsen, T., and Cho-Chung, Y.S. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 6319-6322). Such selective modulation of protein kinase isozyme regulatory subunits was also found in the 8-Cl-cAMP-induced inhibition of both transformation and transforming growth factor alpha (TGF alpha) production in Ki-ras-transformed rat kidney fibroblasts (Tortora, G., Ciardiello, F., Ally, S., Clair, T., Salomon, D. S., and Cho-Chung, Y. S. (1989) FEBS Lett. 242, 363-367). In this work, we have demonstrated that 8-Cl-cAMP antagonizes the TGF alpha effect in TGF alpha-transformed mouse mammary epithelial cells (NOG-8TFC17) at the level of gene expression for cAMP receptor protein isoforms, RI and RII (the regulatory subunits of protein kinase isozymes). Northern blot analysis demonstrated that in the transformed NOG-8TFC17 cells, compared with the nontransformed counterpart NOG-8 cells, the mRNA levels for the RI alpha cAMP receptor protein markedly increased, whereas the mRNA levels for the RII alpha and RII beta cAMP receptor proteins decreased. 8-Cl-cAMP, which induced growth inhibition and phenotypic reversion in NOG-8TFC17 cells, caused an inverse change in the mRNA patterns of the cAMP receptor proteins; RI alpha cAMP receptor mRNA sharply decreased to levels comparable with that of the nontransformed NOG-8 cells, whereas RII beta mRNA increased to a level even greater than that in the NOG-8 cells. In addition, one mRNA species of RII alpha increased, whereas the other RII alpha mRNA species decreased during the treatment. The mRNA level for the catalytic subunit of protein kinase, however, did not change during 8-Cl-cAMP treatment. In addition, 8-Cl-cAMP brought about a reduction in both TGF alpha mRNA and protein levels. These coordinated changes in the expression of the cAMP receptor proteins and TGF alpha were not observed during cis-hydroxyprolineor TGF beta-induced growth inhibition of the NOG-8TFC17 cells. Thus, the antagonistic effect of 8-Cl-cAMP toward TGF alpha-induced transformation involves modulation of the expression of a specific set of cellular genes.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Differential expression of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in two experimental models of liver cell proliferation.

Hepatocyte growth factor, a potent hepatocyte mitogen in vitro, appears to trigger hepatocyte regeneration after partial hepatectomy and after acute liver cell necrosis. Transforming growth factor-alpha and transforming growth factor-beta 1 may also be involved in the control of liver regeneration. In this study we assessed possible roles of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 on liver cell proliferation in vivo, using a model of choline deficiency that is associated with liver cell necrosis and a model of a hypolipidemic agent (4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide) without liver necrosis. Male F344 rats were fed a choline-deficient diet or 0.16% 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 6 and 4 wk, respectively. Rats were killed periodically, and the expression of hepatocyte growth factor messenger RNA in the liver, lung and kidney was determined by Northern-blot analysis. The levels of transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in the liver were also determined. Feeding a choline-deficient diet for 1 to 6 wk led to gradual increases in the levels of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in the liver. Feeding a 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 3 days and 2 wk induced marked enhancement of liver cell proliferation as judged by hepatocyte 5-bromo-2-deoxyuridine incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The effects of epidermal growth factor, transforming growth factors alpha and beta and platelet-derived growth factor on murine palatal shelves in organ culture.

Palatal shelves isolated from day-13 embryonic mice were explanted on to the surfaces of collagen gels either singly or in pairs with their medial edges in contact, and cultured submerged in a 1:1 mixture of Dulbecco's modified Eagle's medium/Ham's F12 medium. The medium was supplemented with either 10 ng/ml epidermal growth factor (EGF), 10 ng/ml transforming growth factor alpha (TGF alpha), 1 ng/ml transforming growth factor beta (TGF beta 1) or 2 ng/ml platelet-derived growth factor (PDGF) all in the presence or absence of 2.5% donor calf serum (DCS). Cultures were terminated after 0, 24, 48 or 72 h and processed for histological and immunocytochemical examination. In serum-free medium and medium supplemented with 2.5% DCS the palatal epithelia differentiated in a manner similar to that seen in vivo (oral, keratinization; nasal, pseudostratified, ciliated columnar cells and medial edge, epithelial degeneration). A similar pattern was obtained in serum-free medium supplemented with either EGF or TGF alpha. However in cultures with either EGF or TGF alpha plus 2.5% DCS present in the medium, medial-edge epithelial degeneration was inhibited and the oral epithelia were more heavily keratinized. The mesenchyme of such cultures stained more intensely for various extracellular matrix molecules. In TGF beta 1-supplemented cultures (with, but especially without, serum supplementation) the epithelia were thin, medial-edge epithelial degeneration was marked, and the fibronectin content of the mesenchyme was increased. PDGF prevented medial-edge epithelial degeneration in the presence, but not in the absence, of serum; mesenchymal extracellular molecules were not as prevalent as with the EGF treatment. These results indicate that exogenous growth factors (including those present in serum) exert effects on organ-cultured mouse palatal shelves in a fashion similar to their effects in cell culture and that controlled physiological levels of such factors may be important in mouse palatal development.

Animals↗

PubMed1985

Transforming growth factors from a human tumor cell: characterization of transforming growth factor beta and identification of high molecular weight transforming growth factor alpha.

Intracellular transforming growth factors (TGFs) were extracted from a human rhabdomyosarcoma cell line and purified to apparent homogeneity by using gel filtration, cation-exchange, and high-performance liquid chromatography. Two types of transforming growth factor activities, TGF-alpha and TGF-beta, were detected. The intracellular polypeptides which belonged to the TGF-alpha family required TGF-beta for full activity in inducing nonneoplastic normal rat kidney fibroblasts to grow in soft agar. These peptides also bound to the membrane receptor for epidermal growth factor. As determined by sodium dodecyl sulfate-polyacrylamide gels, the apparent molecular weight of these intracellular TGF-alpha's was 18 000. Intracellular TGF-beta required either epidermal growth factor or TGF-alpha for stimulation of soft agar growth. The intracellular TGF-beta was purified to homogeneity as judged by a single peak after reverse-phase high-performance liquid chromatography and a single band on a sodium dodecyl sulfate-polyacrylamide gel. The intracellular TGF-beta from the human tumor cell line was similar in all respects tested (migration on sodium dodecyl sulfate-polyacrylamide gels, stimulation of soft agar growth, binding to the membrane receptor for TGF-beta, and amino acid composition) to intracellular TGF-beta from normal human placenta.

Amino Acids↗

PubMed1990

Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor alpha to epidermal growth factor receptors promotes cell proliferation.

The precursor for transforming growth factor alpha, pro-TGF-alpha, is a cell surface glycoprotein that can establish contact with epidermal growth factor (EGF) receptors on adjacent cells. To examine whether the pro-TGF-alpha/EGF receptor pair can simultaneously mediate cell adhesion and promote cell proliferation, we have expressed pro-TGF-alpha in a bone marrow stromal cell line. Expression of pro-TGF-alpha allows these cells to support long-term attachment of an EGF/interleukin-3-dependent hematopoietic progenitor cell line that expresses EGF receptors but is unable to adhere to normal stroma. This interaction is inhibited by soluble EGF receptor ligands. Further, the hematopoietic progenitor cells replicate their DNA while they are attached to the stromal cell layer and become foci of sustained cell proliferation. Thus, pro-TGF-alpha and the EGF receptor can function as mediators of intercellular adhesion and this interaction may promote a mitogenic response. We propose the term "juxtacrine" to designate this form of stimulation between adjacent cells.

Animals↗

PubMed1992

Nucleotide sequence and tissue distribution of mouse transforming growth factor-alpha.

Transforming growth factor-alpha (TGF alpha) is secreted into the medium of the Moloney murine sarcoma virus-transformed 3T3 cell line, 3B11-1C. Using reverse transcription-polymerase chain reaction (RT-PCR), we have amplified, cloned and sequenced a cDNA fragment from this cell line which encodes the full protein-coding region of the mouse TGF alpha precursor. The deduced amino acid sequence (159 residues) differs from that of human TGF alpha at 13 sites and from that of rat at 3 sites. In the mouse, TGF alpha transcripts were detected in a variety of normal adult tissues including two previously unreported sites: the preputial glands and the bladder.

Amino Acid Sequence↗

PubMed1991

Constitutive expression of transforming growth factor alpha does not transform rat thyroid epithelial cells.

To evaluate the role of transforming growth factor alpha (TGF alpha) in transformed rat thyroid epithelial cells, expression and production of TGF alpha were measured in a normal rat thyroid epithelial cell line, FRTL-5, and in the same cells transformed by the Ki-ras oncogene. FRTL-5 cells transformed with Ki-ras exhibit a 5- to 7-fold increase in the levels of TGF alpha-specific mRNA and a 3- to 4-fold enhancement of the amounts of TGF alpha protein in the conditioned medium, as compared with the normal thyroid cells. Although conditioned medium from the Ki-ras transformed FRTL-5 cells or authentic epidermal growth factor or TGF alpha are able to stimulate the anchorage-dependent growth of nontransformed FRTL-5 cells, neither conditioned medium nor the growth factors are able to induce the anchorage-independent growth of these cells in soft agar. FRTL-5 cells were then transfected with an expression vector plasmid containing the human TGF alpha cDNA to directly ascertain if over-expression of this growth factor is able to induce transformation in these cells. The TGF alpha-transfected FRTL-5 clones constitutively produced high amounts of TGF alpha at a level equivalent to or greater than the level found in the conditioned medium from the Ki-ras transformed FRTL-5 clones. Moreover, in contrast to the Ki-ras transformed cells, the TGF alpha transfectants were unable to grow in soft agar, did not form tumors in nude mice, and showed no reduction in the secretion of thyroglobulin. These data demonstrate that unlike Ki-ras, the constitutive expression of biologically active TGF alpha is not entirely sufficient to elicit a transformed phenotype in these cells.

Animals↗

PubMed1987

The genome of Shope fibroma virus, a tumorigenic poxvirus, contains a growth factor gene with sequence similarity to those encoding epidermal growth factor and transforming growth factor alpha.

Degenerate oligonucleotide probes corresponding to a highly conserved region common to epidermal growth factor, transforming growth factor alpha, and vaccinia growth factor were used to identify a novel growth factor gene in the Shope fibroma virus genome. Sequence analysis indicates that the Shope fibroma growth factor is a distinct new member of this family of growth factors.

Amino Acid Sequence↗

PubMed1992

Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.

Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis.

Blotting, Northern↗

PubMed1988

Assessment of biological activity of synthetic fragments of transforming growth factor-alpha.

Transforming growth factor-alpha (TGF-alpha) is a single chain polypeptide hormone of 50 amino acids that stimulates growth of some human cancer cells via an autocrine mechanism. The domain(s) of TGF-alpha that bind and activate its receptor have not been reported. Hydrophilicity plots of TGF-alpha indicate three discrete sequences that are theoretically exposed on the hormone's surface and thus potentially able to interact with the TGF-alpha receptor. Fragments of TGF-alpha encompassing these hydrophilic domains were prepared by using solid-phase peptide synthesis (SPPS) techniques and purified by use of high performance liquid chromotography (HPLC). Assessment of biological activity of the TGF-alpha fragments indicated that none of the fragments significantly inhibited binding of EGF to the receptor, stimulated DNA synthesis of cells, inhibited EGF-induced DNA synthesis of cells, stimulated growth of cells in soft agar, or induced phosphorylation of the receptor or p35 protein. These results indicate that the receptor binding domain of TGF-alpha is not totally encompassed by any of the separate fragments tested and probably is formed by multiple separate regions of TGF-alpha.

Amino Acid Sequence↗

PubMed1991

Autocrine stimulation of interleukin-1 alpha and transforming growth factor alpha production in human keratinocytes and its antagonism by glucocorticoids.

Interleukin-1 (IL-1) and transforming growth factor alpha (TGF alpha) mRNA expression was analyzed in cultured normal human keratinocytes. Keratinocytes constititively express IL-1 mRNA when cultured in keratinocyte growth medium but not in Dulbecco's minimal essential medium containing fetal bovine serum, in which the cells differentiate. The predominant form of IL-1 expressed by keratinocytes is IL-1 alpha. Addition of IL-1 alpha to keratinocytes increased IL-1 alpha and TGF alpha mRNA expression in a dose-dependent manner. TGF alpha induced a similar increase in IL-1 alpha and TGF alpha mRNA in keratinocytes. Hydrocortisone decreased the expression of both IL-1 alpha and TGF alpha mRNA in keratinocytes. These findings document an autocrine mechanism by which IL-1 alpha and TGF alpha can stimulate the proliferation of keratinocytes in the skin. It is proposed that this autocrine loop may be hyperactive in psoriasis. Antagonism of the effects of this autocrine loop may be one of the mechanisms by which glucocorticoids exert clinically useful effects in psoriasis and other diseases of the skin.

Cells, Cultured↗

PubMed1988

Expression of transforming growth factor alpha during development.

Transforming growth factors (TGFs) are polypeptides that are produced by transformed and tumour cells, and that can confer phenotypic properties associated with transformation on normal cells in culture. One of these growth-regulating molecules, transforming growth factor alpha (TGF-alpha), is a 50 amino acid polypeptide that is related to epidermal growth factor (EGF) and binds to the EGF receptor. Previous studies have shown that TGF-alpha is expressed during rodent embryogenesis between 7 and 14 days gestation. To investigate the cellular sites of TGF-alpha mRNA expression during development, we have performed Northern analyses and in situ hybridization histochemistry on the conceptus and maternal tissues at various gestational ages. Contrary to previous reports, both Northern analyses and in situ hybridization histochemistry indicate that TGF-alpha mRNA is predominantly expressed in the maternal decidua and not in the embryo. Decidual expression is induced following implantation, peaks at day 8, and declines through day 15 when the decidua is being resorbed. In situ hybridization revealed that expression of TGF-alpha mRNA is highest in the region of decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and embryo. In addition, we could not detect TGF-alpha mRNA expression in other maternal tissues, indicating that the induction of TGF-alpha transcripts in the decidua is tissue specific, and not a pleiotropic response to changes in hormonal milieu that occur during pregnancy. The developmentally regulated expression of TGF-alpha mRNA in the decidua, together with the presence of EGF receptors in this tissue, suggests that this peptide may stimulate mitosis and angiogenesis locally by an autocrine mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1989

Differential expression of transforming growth factors alpha and beta in rat intestinal epithelial cells.

Expression of transforming growth factor alpha (TGF alpha), and transforming growth factor beta (TGF beta) was assessed in isolated primary rat intestinal epithelial cells as well as a rat intestinal crypt cell-derived cell line (IEC-6). A gradient in TGF beta was present, with high concentrations of a 2.5-kb transcript found in undifferentiated crypt cells and progressively lower amounts of the TGF beta transcript in increasingly differentiated villus cell populations. In contrast, the concentration of 4.5-kb TGF alpha transcript was higher in differentiated villus cells than in mitotically active, undifferentiated populations of crypt epithelial cells. The concentrations of transforming growth factors alpha and beta as determined by radioreceptor binding inhibition assay and direct assessment of transforming growth factor biological activity correlated with Northern blot analysis. Although gradients in the expression of the TGFs were present, equivalent binding was observed in the different intestinal cell populations when assessed with 125I-TGF beta and 125I-EGF (TGF alpha). No EGF transcripts were detected in any intestinal cell population, suggesting that the true ligand of the EGF receptor was TGF alpha. IEC-6 cells expressed both TGF alpha and TGF beta transcripts. In addition to the transcripts identified in the primary intestinal cells, this cell line contained an additional larger TGF alpha transcript (4.8 kb) and smaller TGF beta transcripts (2.2 and 1.8 kb). TGF alpha and TGF beta may play a significant role in the regulation of the balance between proliferative and differentiated cell compartments in the intestinal epithelium through both autocrine and paracrine mechanisms.

Animals↗

PubMed1988

Transforming growth factor alpha in chemically transformed hamster oral keratinocytes.

The cheek pouch of the Syrian hamster is an excellent tissue for the experimental induction of oral cancer by carcinogenic chemicals. Lysate prepared from a cell line (HCPC-1) derived from one of these hamster oral tumors greatly increased the growth of these oral tumor cells in vitro. We now show that the mitogenic substance, transforming growth factor alpha (TGF-alpha), is present in all of the chemically transformed hamster oral tumors examined (in vitro and in vivo). In no adult normal tissue of the Syrian hamster can we detect expression of TGF-alpha. TGF-alpha could be partly or wholly responsible for the mitogenic activity detected in the lysate of the chemically transformed hamster oral keratinocytes. Both normal and chemically transformed hamster oral keratinocytes express the receptor to epidermal growth factor. The consistent detection of TGF-alpha and epidermal growth factor receptor mRNAs in these hamster oral tumor cells suggests that an autocrine growth mechanism might be operative. This hamster cheek pouch oral cancer model can be used for the molecular analysis of how TGF-alpha and epidermal growth factor receptor might be involved in the malignant transformation of epithelial tissues.

9,10-Dimethyl-1,2-benzanthracene↗