Growth factor-regulated pathways in epithelial cell proliferation.
Investigations of the pathways regulating normal growth of epithelial cells have revealed the existence of two major growth-factor signaling cascades required for proliferation. One pathway is activated by IGF-1 or high insulin concentration. The other is triggered by EGF, TGF alpha, or members of the FGF family, including the recently discovered epithelial-cell-specific growth factor, designated keratinocyte growth factor (KGF). Its expression pattern in vivo suggests that KGF plays an important normal physiologic role as a stromal effector of epithelial cell proliferation. Oncogenes, which represent constitutively activated forms of genes critically involved in growth-factor signaling pathways, specifically abrogate the requirement for mitogens of the EGF pathway. Examples of such genes include the erbB/EGF receptor and erbB-2, which encode structurally related receptor proteins and are often amplified and/or overexpressed in epithelial malignancies. Employing reduced stringency hybridization with v-erbB as a probe, we recently identified a third member of this receptor family, designated erbB-3. cDNA cloning revealed a predicted 148-kD transmembrane polypeptide with structural features similar to those of the EGF receptor. Normal erbB-3 expression in keratinocytes and glandular epithelium suggests its physiologic role in these cell types. Moreover, markedly elevated erbB-3 mRNA levels in certain mammary tumor cell lines suggest that increased erbB-3 expression may also play a role in some human epithelial malignancies.
Aaronson
S A
SA
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Rubin
J S
JS
Finch
P W
PW
Wong
J
J
Marchese
C
C
Falco
J
J
Taylor
W G
WG
Kraus
M H
MH
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000502:physiology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D051379:Mice; D009857:Oncogenes / Q000502:physiology
C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D066246:ErbB Receptors