دورية أكاديمية
p38MAPK-activated AKT in HER-2 overexpressing human breast cancer cells acts as an EGF-independent survival signal.
| العنوان: | p38MAPK-activated AKT in HER-2 overexpressing human breast cancer cells acts as an EGF-independent survival signal. |
|---|---|
| المؤلفون: | Diehl KM; University of Michigan Health Systems, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA., Grewal N, Ethier SP, Woods-Ignatoski KM |
| المصدر: | The Journal of surgical research [J Surg Res] 2007 Sep; Vol. 142 (1), pp. 162-9. Date of Electronic Publication: 2007 Jul 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0376340 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-4804 (Print) Linking ISSN: 00224804 NLM ISO Abbreviation: J Surg Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: Philadelphia [etc.] |
| مواضيع طبية MeSH: | Breast Neoplasms/*metabolism , Epidermal Growth Factor/*physiology , Proto-Oncogene Proteins c-akt/*physiology , Receptor, ErbB-2/*metabolism , Signal Transduction/*physiology , p38 Mitogen-Activated Protein Kinases/*metabolism, Breast Neoplasms/genetics ; Breast Neoplasms/physiopathology ; Cell Line, Tumor ; Cell Survival/physiology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics |
| مستخلص: | Background: HER-2 is an epidermal growth factor receptor (EGFR) family receptor tyrosine kinase that is overexpressed in about 30% of human breast cancers correlating with a poor prognosis. Previous work in our laboratory has found that HER-2 overexpression plays a role in growth factor independence, anchorage independence, motility, and invasion of naturally occurring basement membranes. We also found that AKT was activated by p38MAPK in these cells, but this activation did not play a role in invasion. Since AKT has been shown in other systems to be a survival factor, we hypothesized that HER-2 mediated activation of AKT is necessary for growth factor independence. Methods: Human mammary epithelial cells transduced to overexpress HER-2, HER-2, PTEN, and Myr-AKT and the primary breast cancer cell lines SUM-149 and SUM-225 were used to dissect the signaling pathways leading to growth factor independence and anchorage-independent growth in HER-2 overexpressing cells. Results: We found that, in the absence of EGF, p38MAPK-activated AKT is necessary for HER-2 overexpressing cells to survive and to form colonies in soft agar. We show that EGF works as a survival signal in the absence of p38MAPK-mediated activation of AKT. We also show that human mammary epithelial cells expressing a constitutively active AKT do not require EGF for growth or colony formation in soft agar. Conclusions: The data presented here indicate that AKT activation can compensate for EGF-mediated cell survival signals leading to growth factor independence and anchorage-independent growth. |
| المشرفين على المادة: | 62229-50-9 (Epidermal Growth Factor) EC 2.7.10.1 (ERBB2 protein, human) EC 2.7.10.1 (Receptor, ErbB-2) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) |
| تواريخ الأحداث: | Date Created: 20070707 Date Completed: 20071002 Latest Revision: 20141120 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.jss.2007.01.025 |
| PMID: | 17612563 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 0022-4804 |
|---|---|
| DOI: | 10.1016/j.jss.2007.01.025 |