ESTROGEN-RECEPTOR, GROWTH-FACTOR RECEPTOR AND PROTOONCOGENE PROTEIN ACTIVITIES AND POSSIBLE SIGNAL-TRANSDUCTION CROSSTALK IN ESTROGEN-DEPENDENT AND INDEPENDENT BREAST-CANCER CELL-LINES

Citation
As. Mohamood et al., ESTROGEN-RECEPTOR, GROWTH-FACTOR RECEPTOR AND PROTOONCOGENE PROTEIN ACTIVITIES AND POSSIBLE SIGNAL-TRANSDUCTION CROSSTALK IN ESTROGEN-DEPENDENT AND INDEPENDENT BREAST-CANCER CELL-LINES, Journal of submicroscopic cytology and pathology, 29(1), 1997, pp. 1-17
Citations number
40
Categorie Soggetti
Cell Biology",Pathology
ISSN journal
11229497
Volume
29
Issue
1
Year of publication
1997
Pages
1 - 17
Database
ISI
SICI code
1122-9497(1997)29:1<1:EGRAPP>2.0.ZU;2-R
Abstract
Binding of estrogen to its receptor (ER) activates early genes that dr ive responsive cells through the proliferative phase. Earlier studies to evaluate the expression of protooncogenes, growth factors, growth f actor receptor and steroid hormone receptor gene activities in the rat uterine system indicated complex pathways that involve significant 'c rosstalk' between ER-systems and signal transduction pathways (Bhattac haryya et al., 1994). To analyze the interactions between these factor s, we examined two well characterized estrogen dependent (MCF-7) and e strogen independent (MDA-MB-231) human breast cancer cell lines. Antib odies to estrogen receptor, epidermal growth factor receptor, c-Fos, c -Jun, and Ras proteins, protein kinases involved in receptor tyrosine kinase signal transduction pathway, MEK1 and phosphotyrosine were util ized in immunocytochemical localization experiments to evaluate tempor al expression of these factors in response to estrogen treatment. ER, which was diminished in MCF-7 cells grown in estrogen-stripped medium, increased 9-fold in estrogen-reconstituted medium by 120 min. Fos and Jun appeared at nuclear and perinuclear cytoplasmic sites within 60 m in after estrogen treatment in MCF-7 cells. Fos/Jun proteins were prom inent in MDA-MB-231 cells, especially in association with actin filame nts. Immunolabeling studies revealed no EGF-r in MCF-7 cells, while MD A-MB-231 cells contained intense EGF-r labeling in the plasma membrane . Ras protein was prominent in the cytoplasm and at the cell surface w ithin 60 min after treatment of MCF-7 cells with estrogen. Ras was int ense in MDA cells. Similarly, MCF-7 and MDA cells contained high conce ntrations of MEK1 and phosphotyrosine (pTyr) containing proteins in th eir cytoplasm and immunolabeling remained high as long as MCF-7 cells were grown in medium containing estrogen. It is speculated that MEK1 ( cytoplasmic) functioning through Fos/Jun or Myc/Max (nuclear) may regu late the activity of AP-l transcription factor. In all cases however, MEK1 and pTyr protein labeling was more intense in the highly metastat ic and hormone independent MDA-MB-231 breast cancer cells. Results rev ealed signal transduction pathway proteins in ER(+) estrogen dependent cells suggesting possible crosstalk between both receptor pathways du ring the proliferative phase of MCF-7 cells.