The int-2 gene product acts as a growth factor and substitutes for basic fibroblast growth factor in promoting the differentiation of a normal mouse mammary epithelial cell line.
We have investigated the effect of basic fibroblast growth factor (bFGF) and the related int-2 gene on the growth, transformation, and differentiation of HC11 mouse mammary epithelial cells. We show that in HC11 cells infected with int-2 retroviral expression vectors, the int-2 protein can function as a bFGF-like growth factor in stimulating: (a) HC11 cell proliferation in monolayer, (b) anchorage-independent growth in soft agar, and (c) soft agar growth of the bFGF-responsive SW13 tumor cell line. These effects are observed irrespective of whether the int-2 protein is expressed in its wild-type form or is linked to a signal peptide. A candidate bFGF receptor, which is the product of the flg gene and which may recognize the int-2 protein, is expressed at high levels in HC11 cells. Following epidermal growth factor or bFGF priming and subsequent treatment with lactogenic hormones, all of the int-2 infected and the parental HC11 cells synthesize similar levels of beta-casein. However, the autocrine expression of int-2 in HC11 cells abrogates their requirement for either exogenous epidermal growth factor or bFGF priming. These data suggest that, in HC11 cells, the growth factor activity of the int-2 gene is indistinguishable from that of bFGF and does not interfere with the mammary cell differentiation program associated with lactogenesis.
Venesio
T
T
National Cancer Institute, NIH, Bethesda, Maryland 20892.
Taverna
D
D
Hynes
N E
NE
Deed
R
R
MacAllan
D
D
Ciardiello
F
F
Valverius
E M
EM
Salomon
D S
DS
Callahan
R
R
Merlo
G
G
D000362:Agar; D000818:Animals; D002364:Caseins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D004247:DNA / Q000032:analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D015513:Oncogene Proteins / Q000502:physiology*; D012313:RNA / Q000032:analysis; D012016:Reference Values; D014407:Tumor Cells, Cultured
D002364:Caseins; D004273:DNA, Neoplasm; D006133:Growth Substances; D015513:Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D012313:RNA; D000362:Agar; D004247:DNA