Yokoyama M, Funatomi H, Kobrin M, Ebert M, Friess H, Buchler M, Korc M
UNIV CALIF IRVINE,DEPT MED,DIV ENDOCRINOL DIABET & METAB,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. UNIV BERN,INSELSPITAL,DEPT VISCERAL & TRANSPLANTAT SURG,CH-3010 BERN,SWITZERLAND.
Int J Oncol. 1995 Oct;7(4):825-9. doi: 10.3892/ijo.7.4.825.
Human pancreatic ductal adenocarcinomas overexpress the epidermal growth factor (EGF) receptor. Betacellulin is a mitogenic polypeptide that binds and activates this receptor. To determine whether betacellulin has a role in human pancreatic cancer, we studied its expression in cultured human pancreatic cancer cell lines and in normal and cancerous pancreatic tissues. Five of 6 pancreatic cancer cell lines expressed the 3 kb betacellulin mRNA moiety, T3M4, MiaPaCa-2 and COLO-357 cells exhibiting the highest expression levels. EGF, heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) increased betacelullin mRNA levels. Only 2 of 15 normal samples and 1 of 10 cancer samples failed to exhibit the betacellulin transcript. Densitometric analysis of the autoradiographs revealed a 7.5-fold increase in betacellulin mRNA levels in the cancer tissues by comparison with the normal tissues. By in situ hybridization, the duct-like cancer cells exhibited many betacellulin mRNA in situ hybridization grains. These findings indicate that human pancreatic cancer cells express betacellulin in culture and in vivo, and suggest that this EGF-like ligand may participate in aberrant autocrine and paracrine activation of the EGF receptor in human pancreatic cancer.
人类胰腺导管腺癌过度表达表皮生长因子（EGF）受体。β细胞ulin是一种有丝分裂原性多肽，它能结合并激活该受体。为了确定β细胞ulin在人类胰腺癌中是否起作用，我们研究了它在培养的人类胰腺癌细胞系以及正常和癌性胰腺组织中的表达情况。6个胰腺癌细胞系中有5个表达3 kb的β细胞ulin mRNA部分，其中T3M4、MiaPaCa - 2和COLO - 357细胞的表达水平最高。表皮生长因子（EGF）、肝素结合表皮生长因子样生长因子（HB - EGF）和碱性成纤维细胞生长因子（bFGF）可增加β细胞ulin mRNA水平。15个正常样本中有2个、10个癌样本中有1个未检测到β细胞ulin转录本。对放射自显影片的密度分析显示，与正常组织相比，癌组织中β细胞ulin mRNA水平增加了7.5倍。通过原位杂交，导管样癌细胞显示出许多β细胞ulin mRNA原位杂交颗粒。这些发现表明，人类胰腺癌细胞在培养和体内均表达β细胞ulin，并提示这种表皮生长因子样配体可能参与人类胰腺癌中表皮生长因子受体异常的自分泌和旁分泌激活。
