Accession Number : ADA501595


Title :   Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone


Descriptive Note : Final rept. 1 Mar 2006-28 Sep 2008


Corporate Author : COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO


Personal Author(s) : Harrell, Joshua C ; Horwitz, Kathryn B


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a501595.pdf


Report Date : Oct 2008


Pagination or Media Count : 38


Abstract : Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. We developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors were tracked in living mice by whole-body imaging, and macrometastases or micrometastases were detected by intravital imaging or fluorescence microscopy. Tumor growth was estrogen dependent and progesterone had minimal impact on tumor growth or metastasis. To determine if the LN microenvironment alters estrogendependent gene expression, we developed a unique model to identify estradiol regulated genes in ER+ breast tumors and LN metastases. Fluorescent ER+ MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and PR induction were deficient in LN metastases, indicating that ER transcriptional activity was altered in the LN. Cancer cells from estradiol treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both.. We propose that the LN microenvironment alters estradiol signaling and contributes to antiestrogen resistance.


Descriptors :   *BREAST CANCER , GENES , RECEPTOR SITES(PHYSIOLOGY) , LYMPH NODES , TRANSCRIPTION(GENETICS) , ESTROGENS , METASTASIS , PROTEINS , PROGESTERONE


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE