Effect of epidermal growth factor (EGF) on a newly established head and neck squamous carcinoma cell line

A new cell line designated 584A2 has been recently established from a patient with squamous cell carcinoma of the larynx. Cytogenetic analysis of the cell line revealed multiple copies of chromosome 7, as well as a homogeneous staining region (HSR) on one chromosome 7. Since overexpression of epidermal growth factor (EGF) cell surface receptors (EGFr) often occurs in other squamous carcinoma cell lines, it was predicted that 584A2 might overexpress EFGr. This was confirmed by: (1) metabolic labeling, with subsequent immunoprecipitation of EGFr and comparing autoradiographs to a cell line without an HSR and fewer copies of chromosome 7, and (2) performing EGF binding assays with Scatchard analysis. Since overexpression of EGFr correlates with an inhibitory effect of EGF on cell culture, the biological effects of EGF on 584A2 were examined in this study. At 5 ng/ml (serum-free medium), EFG stimulated incorporation of [3H] thymidine into trichloroacetic acid-precipitable material compared with controls. Incorporation increased between days 0 to 1 and 1 to 2 days with a 6- to 7-fold maximum. Dose-response studies (0 to 100 ng/ml) indicated maximum incorporation (6- to 7-fold) occurred between 0.1 ng/ml and 1.0 ng/ml. Cell growth was monitored over 7 days and, during this time, 5 ng/ml EGF produced a 10- to 12-fold increase in absolute cell numbers when compared with controls. We concluded that, unlike other squamous carcinoma lines with elevated EGFr, EGF stimulates rather than inhibits 584A2 cell proliferation.     

Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies

The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas.     

Epidermal growth factor stimulation and metastatic rate in human pancreatic carcinoma cell lines

Pancreatic carcinoma is usually a fatal disease with most patients dying of metastases. We have developed several pancreatic carcinoma cell lines that have varying metastatic abilities in a splenic injection/liver metastasis model. Epidermal growth factor (EGF) is a mitogen to most cell types with increased levels of EGF receptor. The parent cell line (COLO-357) of the pancreatic carcinoma cell lines used in this study has been shown to have a high number of EGF receptors per cell. We studied the relationship between the mitogenic responsiveness to EGF and the metastatic rate of each of the cell lines. Three of the six cell lines were significantly stimulated by EGF as determined by an increase in cell number over the course of 4 days, and three of the cell lines were not. There was no correlation between metastatic rate and EGF responsiveness. Further work will be needed to determine if there is any relationship between growth factors and their receptors and tumor metastasis with these pancreatic cancer cell lines.     

Transforming growth factor-beta inhibits the growth of renal cell carcinoma in vitro

Transforming growth factor-beta (TGF-beta) is a bifunctional growth regulatory hormone which inhibits the growth of many normal and neoplastic epithelial cell lines in monolayer culture. Endogenous and exogenous TGF-beta may influence cell proliferation through autocrine and paracrine binding to specific TGF-beta receptors. Growth effects of TGF-beta on human renal cell carcinoma cell lines have not been thus far described. We have studied the effects of TGF-beta on one renal tumor-derived (UOK-39) and one established (SKRC-7) renal cell carcinoma cell line. Exogenous addition of biologically active TGF-beta to cell cultures at concentrations between two and five ng./ml. inhibited the anchorage-dependent growth of UOK-39 by 75% and SKRC-7 by 44%, relative to controls. Low numbers of high affinity TGF-beta receptors were identified on both cell lines in 125I-TGF-beta binding assays. UOK-39 cells bound radiolabeled TGF-beta with higher affinity than SKRC-7 cells, but had fewer receptor sites, by Scatchard analysis of binding data. These results suggest that TGF-beta inhibits proliferation of renal carcinoma cells in vitro which may be mediated through binding of exogenous TGF-beta to functional TGF-beta receptors on the cell surface.     

Inhibition of chemomigration of a human prostatic carcinoma cell (TSU-pr1) line by inhibition of epidermal growth factor receptor function

Chemoattractants expressed at bony sites and pelvic lymph nodes are thought to promote the preferential metastasis of human prostate tumor cells to these organs. Epidermal growth factor (EGF) is a potent chemoattractant for several human metastatic prostate tumor cell lines, including the TSU-pr1 cell line, and EGF has been localized to the stroma of both bony sites and pelvic lymph nodes in humans. Hence, we investigated whether the TSU-pr1 cell line expresses a functional EGF receptor (EGFR), which when antagonized reduces EGF-mediated chemomigration of this cell line. In this context, the EGFR immunoprecipitated from cell lysates of TSU-pr1 cells comigrated with the EGFR from A431 cells at a molecular weight of 170 kD. Addition of human EGF (hEGF) to the TSU-pr1 cells for 5 min stimulated the dose-dependent biphasic phosphorylation of the EGFR, with maximal stimulation of EGFR phosphorylation occurring at 2 ng/ml hEGF. In addition, treatment of hEGF-stimulated (2 ng/ml) TSU-pr1 cells with 0.5 μg/ml anti-hEGFR monoclonal antibody or 100 nM staurosporine inhibited EGFR phosphorylation. Conversely, as negative controls, treatment of hEGF-stimulated (2 ng/ml) TSU-pr1 cells with K252a or dimethyl sulfoxide (DMSO) vehicle did not inhibit EGFR phosphorylation. TSU-pr1 cells were stimulated to migration in 4 hr across Boyden chambers in response to 10 ng/ml hEGF. Treatment of the TSU-pr1 cells with anti-hEGFR monoclonal antibody inhibited in a dose-dependent manner the chemomigration of the TSU-pr1 cells across Boyden chambers. Similarly, treatment of the TSU-pr1 cells with staurosporine inhibited in a dose-dependent manner the chemomigration of the TSU-pr1 cells across Boyden chambers. These results demonstrate that antagonists of hEGF-mediated hEGFR phosphorylation also antagonize chemomigration of the TSU-pr1 cells across Boyden chambers, suggesting that antagonists of the EGFR in prostate cancer may be useful in the treatment of metastatic disease. © 1996 Wiley-Liss, Inc.     

Role of transforming growth factor-alpha in human prostate cancer cell growth

Because of the influence of transforming growth factor-alpha (TGF alpha) on the cell growth in other cancer cell systems, we investigated the growth-regulatory role of TGF alpha in human prostate cancer cells. TGF alpha (5 ng/ml) stimulated LNCaP cell growth in monolayer to 60% of the level seen with dihydrotestosterone (DHT). Both DHT and TGF alpha increased cloning in soft agar twofold above that in controls. Metabolism of thymidine and uridine was also increased as evidenced by increased uptake of these macromolecule precursors. In addition, intracellular signalling as indicated by phosphatidyl inositol turnover was also increased by TGF alpha and DHT. Conditioned media contained TGF alpha by radioimmunoassay (RIA), transforming activity by rat kidney fibroblast (NRK) colony formation, and epidermal growth factor (EGF) receptor competable activity by radioreceptor assay. EGF receptors were present by binding assay and immunoprecipitation. These data demonstrate the presence of an autostimulatory growth loop in hormone-responsive human prostate cancer cells.     

Epidermal growth factor in the urine of patients with renal cell carcinoma and bladder tumor]

We evaluated the concentrations of immunoreactive epidermal growth factor (EGF) in urine samples from 14 patients with renal cell carcinoma, 16 patients with bladder tumor and 43 non-malignant controls by using radioimmunoassay. In the non-malignant controls, urinary EGF excretion significantly decreased with age (r = -0.46, p less than 0.01), and females excreted significantly more EGF than males [16.3 +/- 7.6 and 9.9 +/- 6.0 (mean +/- SD) ng/mg.creatinine; p less than 0.05]. There was no significant difference between urinary EGF excretion in the patients with renal cell carcinoma and non-malignant controls matched for sex and age (15.9 +/- 12.0 and 14.5 +/- 7.9 ng/mg.creatinine). The difference in excretion of EGF between the patients with bladder tumor and non-malignant controls also was not significant (9.9 +/- 5.6 and 11.7 +/- 7.0 ng/mg.creatinine). These findings indicate, that urine EGF has little usefulness as a tumor marker for renal cell carcinoma and bladder tumor.     

Bladder cancer cells express functional receptors for granulocyte-colony stimulating factor.

The effects of human recombinant granulocyte-colony stimulating factor (G-CSF) on the growth of cultured human bladder cancer cells and G-CSF receptor on these cells were investigated. Human bladder cancer cell lines, KU-1 or NBT-2, were incubated with and without G-CSF. At 48 hours, 3H-thymidine uptake of both cells was significantly higher with G-CSF (one ng./ml., 10 ng./ml.) than that of control without G-CSF (p less than 0.05). The binding of 125I-labeled KW-2228, a muteins of G-CSF, to KU-1 and NBT-2 was inhibited by unlabeled KW-2228 in a dose-dependent manner. These results demonstrated that G-CSF stimulates the clonal growth of human bladder cancer cells by binding to its specific receptors.     

Inhibition of head and neck squamous cell carcinoma cell lines by transforming growth factor-β

Transforming growth factor-β is known to be a potent autocrine growth inhibitor produced by a wide variety of cells, including cells of the immune system. Other investigators have noted that the growth of nontransformed keratinocytes is inhibited by transforming growth factor-β, whereas various carcinoma cell lines are resistant to these effects. Head and neck squamous cell carcinoma cells are known to have surface receptors for this cytokine. We thus assessed the effect of transforming growth factor-β on the growth of head and neck squamous cell carcinoma cell lines. Four head and neck squamous cell carcinoma cell lines were incubated with varying concentrations of transforming growth factor-β, and cytotoxicity was evaluated with a methylene blue colorimetric assay. After culturing in transforming growth factor-β for 4 days, inhibition of growth was detected in CAL-27 (maximal inhibition at 5.0 ng/ml), UMSCC-1, and UMSCC-19 (maximal inhibition at 50 ng/ml) cell lines. One other cell line, UMSCC-8 was found resistant to the inhibitory effects of transforming growth factor-β. Kinetics analysis experiments revealed minimal inhibition before day 2 of incubation, at which time inhibition increased linearly to day 4. Assessment of double-stranded DNA fragmentation suggested that DNA fragmentation occurs before significant cytotoxicity. Electron microscopic analysis and gel electrophoresis of extracted DNA revealed morphologic features consistent with apoptotic cell death. Our findings indicate that transforming growth factor-β significantly inhibits the growth of head and neck squamous cell carcinoma cell lines by inducing apoptotic cell death. (OTOLARYNGOL HEAD NECK SURG 1995;112:728-34.)     

Study on in vitro invasive potential of renal cell carcinoma cell lines and effect of growth factors (EGF and TGF-beta 1) on their in invasions

Renal cell carcinomas (RCCs) frequently metastasize to distant organs in their clinical course. However, the mechanism of the metastasis had not been fully elucidated. In vitro invasion assay has been reported to be a rapid method for the evaluation of the invasive potential of various malignant cells. In vitro invasive potential of RCC has not been investigated by this method. Thus, in the present study, we first attempted to characterize the in vitro invasive potential of four human RCC cell lines which had been established in our institute. Secondly, we investigated the influence of two growth factors (EGF, TGF-beta 1) on the invasive potential of these cell lines when the two factors were applied as chemoattractants. SMKT-R-3 and R-4 cell lines showed more cell penetration through Matrigel than SMKT-R-1 and R-2 cell lines, suggesting that the former cell lines have higher invasive potential. While invasive potential varied in each cell line, it was enhanced by EGF in all cell lines. However, TGF-beta 1 suppressed the invasive potential of all four cell lines. These results suggest that two factors have different actions on the invasion of RCCs.     

EPIDERMAL GROWTH FACTOR BINDING BY MEMBRANES OF HUMAN RENAL CELL CARCINOMAS: ESTABLISHMENT OF AN EPIDERMAL GROWTH FACTOR RECEPTOR ASSAY FOR CLINICAL USE

In order to quantitate epidermal growth factor receptors (EGFR) in human renal cell carcinoma (RCC) tissues, the binding of isotope-labeled epidermal growth factor (¹²⁵I-EGF) to pooled membrane samples from human RCC was studied. Specific EGF binding to membranes at 4C reached a plateau after 2 h of incubation and remained constant up to 8 h; specific binding at 25C reached a plateau after 30 min of incubation, then decreased gradually. ¹²⁵I-EGF binding to the membrane was displaced by both EGF and transforming growth factor-aL, but not by insulin and basic fibroblast growth factor. Scatchard analysis of the specific EGF binding generated a straight line, indicating a single class of binding sites for EGF, with a dissociation constant (Kd) of 21.1 times10¹⁰M and a maximum number of binding sites of 57.2fmol/mg membrane protein. When the protein concentration in the incubation medium was adjusted from 0.71mg/ml to 2.84 mg/ml, Scatchard analysis revealed identical Kd values, and the maximum number of binding sites was proportional to the protein concentration. These results demonstrate the presence of EGFR on RCC membranes and indicate that these receptors can be studied quantitatively.     

Partial purification of a major type of rat prostatic growth factor: characterization as an epidermal growth factor-related mitogen

The dorsolateral prostate of rats contains a mitogen that shares several properties with epidermal growth factor (EGF), which was designated as prostatic EGF-related mitogen (PEM). PEM was purified about 2,100-fold using molecular-sieve and ion-exchange chromatography. Final preparation stimulated DNA synthesis in BALB/c 3T3 cells at a concentration as low as 1.5 ng/ml and competed with 125I-EGF for binding to cell surface receptors. PEM had a molecular weight of about 14,000 and an isoelectric point of about 4.5, being heat- and acid-stable but inactivated by dithiothreitol. The primary cultured rat dorsolateral prostate epithelial cells required EGF for maximum growth. Partially purified PEM fully substituted for EGF in the primary culture system at a concentration as low as 90 ng/ml. However, the activity of PEM was hardly suppressed by antimouse EGF antiserum. These findings suggest that PEM is a member of the EGF family but has a higher molecular weight (high molecular weight EGF).     

Changes in epidermal growth factor receptor expression in human bladder cancer cell lines following interferon-alpha treatment

PURPOSE: We examined the regulation of epidermal growth factor (EGF) receptor (EGFR) expression in human bladder cancer cell lines by interferon-alpha (IFN-alpha), the ability of IFN-alpha to inhibit cell proliferation and the sensitivity of IFN-alpha pretreated cells to EGF. MATERIALS AND METHODS: Cell proliferation was determined using crystal violet colorimetric and clonogenic assays. EGFR expression was measured by flow cytometry using specific antibody or ligand binding approaches. RESULTS: After IFN-alpha (100 IU/ml) treatment cell surface EGFR expression was upregulated in 6 of 11 and down-regulated in 2 of 11 bladder cancer cell lines. The over expression of cell surface EGFR peaked within 48 to 96 hours and increased by 35% to 241% in individual cell lines. High level cell surface EGFR correlated with intracellular EGFR expression. Cell growth inhibition by IFN-alpha coexisted with EGFR over expression in the 6 lines. IFN-alpha treated cells remained sensitive to EGF treatment. CONCLUSIONS: IFN-alpha transiently up-regulates EGFR expression and inhibits in vitro growth in some human bladder cancer cells. IFN-alpha does not prevent EGFR from binding EGF or signal transduction via the EGF-EGFR pathway. This may have clinical implications for improving treatment based on EGFR targeting in select patients with bladder cancer.     

Intravesical suramin: a novel agent for the treatment of superficial transitional-cell carcinoma of the bladder

Summary Patients with recurrent or high-grade superficial transitional-cell carcinoma of the bladder that has recurred after intravesical chemotherapy are at increased risk for tumor invasion and metastases. Intravesical chemotherapy is a minimally invasive technique that allows high doses of therapeutic agents to be delivered directly to the malignancy, doses that would not be tolerated systemically. In vitro studies demonstrate suramin's significant efficacy against transitional-cell carcinoma cell lines at relatively low doses. Humans treated with similar doses delivered in a systemic fashion have experienced no bladder toxicity. Suramin has been shown to block the binding of epidermal growth factor (EGF) to its receptors, which are found in large amounts in bladder cancers. Because a significant association has been found between the number of EGF receptors on a bladder-cancer cell and its sensitivity to suramin, transitional-cell carcinoma could potentially be very responsive to such therapy. On the basis of these findings, a phase I escalating-suramin-dose study is currently being conducted.     

基因重组人生长激素对体外培养的肝癌细胞增殖的影响及配体调控

目的 了解基因重组人生长激素(rhGH)对体外培养的Bel-7402细胞增殖的影响,并探讨rhGH对肝癌细胞生长激素受体(GHR)的调控作用.方法 分别采用肿瘤细胞计数、MTT比色法和集落形成实验等方法 了解Bel-7402细胞株在不同浓度rhGH(0、1、10、100、1000、10 000 ng/ml)作用下的药物敏感性,计算细胞生长率;用3H-TdR掺入法研究肿瘤细胞DNA代谢情况;应用放射配体法了解Bel-7402细胞GHR的表达,以及rhGH在上述浓度下对肝癌细胞GHR的影响.结果 rhGH对体外培养的Bel-7402细胞的生长有一定程度促进作用,表现为rhGH在100 ng/ml浓度下促进肝癌细胞增殖较为显著,rhGH在其他浓度(1、10、1000、10000 ng/ml)的部分时段,对肝癌细胞的增殖虽亦有一定程度的促进作用,但总体效果较rhGH在100 ng/ml浓度时弱;放射配体法发现Bel-7402细胞表达GHR,在rhGH作用后24 h,Bel-7402细胞GHR的位点数量(103个/细胞)在10、100 ng/ml组较对照组显著增加,在10000ng/ml组较对照组显著减少.结论 一定浓度范围rhGH对Bel-7402细胞的增殖有促进作用,原因可能与Bel-7402细胞表达GHR有关;同时rhGH对Bel-7402细胞的GHR有一定调控作用.     

神经生长因子受体p75在膀胱癌组织和缺氧条件下膀胱癌T24细胞株中的表达

目的 探讨神经生长因子受体p75(p75NGFR)在膀胱癌组织中的表达及缺氧条件下在膀胱癌细胞表达的变化.方法 免疫组织化学方法检测107例膀胱癌组织标本(男85例,女22例,平均年龄61岁;T117例、T2 77例、T3～T4 13例;病理分级Ⅰ～Ⅱ级75例、Ⅲ～Ⅳ级32例)和24例转移淋巴结组织标本中p75NGFR的表达,癌旁正常黏膜组织50例为对照.选取膀胱移行细胞癌T24细胞株,免疫组织化学、半定量RT-PCR方法检测常规氧分压和微缺氧条件下 p75NGFR在细胞株中的表达.结果 107例膀胱癌组织标本中p75NGFR阳性表达46例(43.0%),正常对照组标本均为阴性表达.p75NGFR阳性表达率与患者性别、年龄、肿瘤组织学分级和分期无相关性(x2值分别为1.509、3.759、0.011和2.324,P值均0.05).24例转移淋巴结组织标本中p75NGFR阳性表达5例(20.8%),与膀胱癌组织标本阳性率比较差异有统计学意义(r=0.077,P<0.05).微缺氧条件下第3天T24细胞株的p75NGFR mRNA吸光度值为0.52±0.07,正常对照组为0.91±0.01,组间差异有统计学意义(P<0.05).结论 膀胱癌组织中p75NGFR表达与淋巴结转移呈负相关;微缺氧条件下p75NGFR mRNA在膀胱癌细胞株中的表达降低.     

Modulation of in vitro cell growth of human and murine urothelial tumor cell lines under the influence of interleukin-3, granulocyte-, macrophage- and granulocyte-colony-stimulating factor

Summary To elucidate possible growth-modulating effects of interleukin 3 (IL-3), granulocyte-macrophagecolony-stimulating factor (GM-CSF) and granulocytecolony-stimulating factor (G-CSF), human transitional cell carcinoma (TCC) cell lines T24, RT112, EJ and 647V were solitarily and continuously exposed to these hematopoietic growth factors at concentrations of 1–100 ng/ml. The murine line MBT-2 was used as a negative and the colon carcinoma cell line HTB38 as a positive control, because of species specificity and known proliferation in response to growth factors, respectively. In the T24 TCC-line solitary and continuous exposure to IL-3, GM-CSF and G-CSF at the highest concentration of 100 ng/ml led to a significant proliferation of cell growth in vitro. Significant proliferation in the RT112 line was only achieved with continuous exposure to IL-3 and GM-CSF (100 ng/ml); G-CSF failed to induce growth modulation in the RT 112 line. No significant proliferative effect of any of cytokines administered was observed in the 647V line. Exposure of the EJ line to cytokines at the highest activity levels had a proliferative effect only in suboptimal growth conditions.Supported by A. Krupp von Bohlen und Halbach-Stiftung, Essen     

Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.     

Fas配体在泌尿生殖肿瘤细胞系及肾癌组织中的表达

目的 明确Ｆａｓ配体在泌尿生殖肿瘤细胞系及肾癌组织中的表达情况。方法 采用免疫细胞化学和反转录ＰＣＲ（ＲＴ－ＰＣＲ）法检测膀胱癌（Ｔ２４、ＢＩＵ－８７、ＥＪ）、肾癌（ＧＲＣ－１、ＲＣＣ－９４９）、前列腺癌（ＰＣ－３Ｍ）及１０例肾癌组织上Ｆａｓ配体的表达。结果 免疫细胞化学方法检测细胞系中Ｆａｓ配体表达于ＢＩＵ－８７、ＲＣＣ－９４９和ＧＲＣ－１细胞,而以ＢＩＵ－８７和ＲＣＣ－９４９细胞系表达较强,在     

Epidermal growth factor receptor gene amplification and expression in head and neck cancer cell lines

We studied epidermal growth factor receptor (EGFR) gene amplification and expression in 11 early passage human head and neck carcinoma cell lines. Three cell lines demonstrated EGFR gene amplification and 10 lines showed an increase in EGFR mRNA when compared with normal keratinocytes, placenta, and a human skin carcinoma cell line. The effects of EGF on growth in 6 head and neck carcinoma cell lines was also studied. Growth inhibition at a concentration of 20 ng/mL was observed in one cell line but had no effect on growth in 5 cell lines. An increase in EGFR may be important in the etiology of, or progression of, head and neck carcinoma although the mechanisms need to be elucidated by further study.