Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells.
The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.
Cassoni
P
P
Department of Biomedical Sciences and Oncology, University of Turin, Italy.
Sapino
A
A
Haagensen
D E
DE
Naldoni
C
C
Bussolati
G
G
D001053:Apolipoproteins; D053399:Apolipoproteins D; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006023:Glycoproteins; D006801:Humans; D026901:Membrane Transport Proteins; D008934:Mitogens / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D008934:Mitogens; D009363:Neoplasm Proteins; C488892:PIP protein, human; D012333:RNA, Messenger