TY - JOUR
T1 - Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells
AU - Lehtola, L
AU - Partanen, Juha
AU - Sistonen, L
AU - Korhonen, J
AU - Wärri, A
AU - Härkönen, P
AU - Clarke, R
AU - Alitalo, K
PY - 1992/2/20
Y1 - 1992/2/20
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Base Sequence
KW - Breast Neoplasms/genetics
KW - Cloning, Molecular
KW - Gene Expression
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - Humans
KW - Molecular Sequence Data
KW - Oligodeoxyribonucleotides/chemistry
KW - Polymerase Chain Reaction
KW - Protein Kinase C/genetics
KW - Protein Kinases/genetics
KW - Protein Serine-Threonine Kinases
KW - Protein-Tyrosine Kinases/genetics
KW - Proto-Oncogene Mas
KW - RNA, Messenger/genetics
KW - RNA, Neoplasm/genetics
KW - Receptors, Cell Surface/genetics
KW - Receptors, Fibroblast Growth Factor
KW - Sequence Alignment
KW - Steroids/pharmacology
KW - Tumor Cells, Cultured
U2 - 10.1002/ijc.2910500419
DO - 10.1002/ijc.2910500419
M3 - Article
C2 - 1311287
SN - 0020-7136
VL - 50
SP - 598
EP - 603
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -