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The role of the HER-2/neu oncogene in gynecologic cancers
1Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Objective:
The HER-2/neu proto-oncogene (also known as c-erbB2, neu, and HER2) encodes a 185-kDa transmembrane glycoprotein with intrinsic tyrosine kinase activity that resembles the receptor for epidermal growth factor. Aberrant HER-2/neu protein overexpression occurs in human gynecologic adenocarcinomas, including those of the ovary, endometrium, breast, fallopian tube, and cervix, and is secondary to gene amplification and/or overexpression of the p185HER2 protein.
Methods:
A Medline literature search revealed numerous studies on HER-2/neu and tumor biology, cancer prognosis, and therapeutic targeting. We present a review of the literature pertinent to gynecologic malignancies.
Results:
Overexpression of HER-2/neu was found to be a poor prognostic factor for survival from advanced-stage ovarian cancer, node-positive breast cancer, and endometrial cancer. Although a specific ligand has not been definitively identified, HER-2/neu may have unusually complex activation pathways because it can form both homodimeric and heterodimeric associations with other related receptor proteins. Preliminary findings suggest that serum HER-2/neu levels may be used as a tumor marker in a subset of patients with tumors that overexpress the HER-2/neu receptor. Receptor-targeted therapeutics currently being studied include the use of receptor antibodies, liposomally delivered antisense DNA, antigen-activated cytotoxic lymphocytes, and adenovirus-mediated E1A delivery to overexpressing tumor cells.
Conclusion:
HER-2/neu appears to play an important role in the biologic behavior of ovarian, endometrial, and breast cancers and holds potential as a target for oncogene-directed therapies.
Insights
The HER-2/neu proto-oncogene is overexpressed in gynecologic cancers, indicating a poor prognosis. This protein shows potential as a therapeutic target for oncogene-directed therapies in ovarian, endometrial, and breast cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The HER-2/neu proto-oncogene encodes a transmembrane glycoprotein with tyrosine kinase activity.
- Aberrant HER-2/neu protein overexpression is observed in various gynecologic adenocarcinomas, including ovarian, endometrial, breast, fallopian tube, and cervical cancers.
- This overexpression is linked to gene amplification or increased p185HER2 protein levels.
Purpose of the Study:
- To review the literature on HER-2/neu's role in gynecologic malignancies.
- To explore HER-2/neu's implications in tumor biology, prognosis, and therapeutic targeting.
Main Methods:
- A comprehensive Medline literature search was conducted.
- The review focused on studies related to HER-2/neu and gynecologic cancers.
Main Results:
- HER-2/neu overexpression is a poor prognostic indicator for advanced ovarian, node-positive breast, and endometrial cancers.
- HER-2/neu exhibits complex activation pathways, potentially involving homodimeric and heterodimeric associations.
- Preliminary data suggest serum HER-2/neu levels may serve as a tumor marker in specific patient subsets.
Conclusions:
- HER-2/neu plays a significant role in the biological behavior of ovarian, endometrial, and breast cancers.
- The HER-2/neu receptor presents a promising target for oncogene-directed therapies.
- Ongoing research includes receptor antibodies, antisense DNA, cytotoxic lymphocytes, and adenovirus-mediated E1A delivery.