Pak1 expression increases tamoxifen resistance in breast cancer patients

May 16, 2006

A protein that activates estrogen receptors in breast cancer may play a role in resistance to therapeutic effects of anti-estrogen tamoxifen treatment, according to a study in the May 17 Journal of the National Cancer Institute.

Pak 1 is a member of a family of proteins involved in many cell functions, such as gene expression, cell movement, and cell death. Previous studies have suggested that the presence of this protein may lead to more invasive breast cancer.

Goran Landberg, M.D., Lund University in Malmö, Sweden, and colleagues examined Pak1 expression in 403 premenopausal women with breast cancer. The women participated in a clinical trial where they were randomly assigned to receive tamoxifen therapy or no treatment. The authors examined whether tumor levels of Pak1 were associated with the women's chances of breast cancer recurrence and the effects of tamoxifen therapy.

The authors found that increased Pak1 expression was associated with increased resistance to tamoxifen therapy for women with estrogen receptor positive breast cancer. Patients with ER-positive tumors and low levels of Pak1 had longer survival without tumor recurrence than patients who did not receive treatment. Overexpression of certain types of Pak1 was associated with decreased response to tamoxifen therapy.

The authors write, "Overall, our observations suggest that Pak1 activation and nuclear localization contribute to the reduced tamoxifen sensitivity that has been observed in some breast tumor cells. Therapies that target Pak1 expression or activity may therefore represent a strategy to increase the endocrine treatment response in breast cancer."

In an accompanying editorial, V. Craig Jordan, Ph.D., D.Sc., of Fox Chase Cancer Center in Philadelphia, discusses what is known about resistance to tamoxifen therapy. He writes, "The clinical correlations reported by Holm et al. indicate that packing tumor cell nuclei with Pak can perturb tamoxifen's action. The tumor, once "Paked up", has no alternative but to grow."
-end-
Contacts:

Article: Kristen Lindel, Kristen.lindel@med.lu.se, and Johanna Sandahl, Johanna.sandahl@med.lu.se
Editorial: Karen Mallet, 215-728-2700, karen.mallet@fccc.edu

Citations:

Article: Holm C, Rayala S, Jirstrom K, Stal O, Kumar R, Landberg G. Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients. J Natl Cancer Inst 2006; 98:671-680.
Editorial: Jordan VC. Pak up your breast tumor - and grow! J Natl Cancer Inst 2006; 98: 657-659.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Journal of the National Cancer Institute

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.