Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells.
The MCF-7 cell line is a hormone-responsive human breast-cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF-7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGF alpha and IGF-I and their receptors. We have amplified and cloned tyrosine-kinase-related sequences from the MCF-7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF-7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast-cancer cells. A putative tyrosine-kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen-responsive tumor cell lines. However, no estrogen-dependent regulation of any of the novel tyrosine-kinase receptor mRNAs was found in any of the cell lines including the MCF-7 or ZR-75-I cells, where the expression of the neu proto-oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast-cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis.
Lehtola
L
L
Department of Pathology, University of Helsinki, Finland.
Partanen
J
J
Sistonen
L
L
Korhonen
J
J
Wärri
A
A
Härkönen
P
P
Clarke
R
R
Alitalo
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D003001:Cloning, Molecular; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor; D016415:Sequence Alignment; D013256:Steroids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D013256:Steroids; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C