Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells.
BACKGROUND
Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin.


METHODS
Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75.


RESULTS
We found the cell adhesion protein desmoplakin to be upregulated by progesterone - a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines.


CONCLUSIONS
Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action.
Pang
Haiyan
H
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Rowan
Brian G
BG
Al-Dhaheri
Mariam
M
Faber
Lee E
LE
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D051180:Desmoplakins; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011374:Progesterone / Q000502:physiology*; D011397:Promegestone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects
D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D009363:Neoplasm Proteins; D011374:Progesterone; D004815:Epidermal Growth Factor; D011397:Promegestone