Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 79, Issue 3, Pages 287-299Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1024031731269
Keywords
breast cancers; estrogens; ligand-independence; progesterone receptors; xenografts
Categories
Funding
- NCI NIH HHS [CA26869] Funding Source: Medline
- NIDDK NIH HHS [DK 48238] Funding Source: Medline
Ask authors/readers for more resources
Sixty to seventy percent of all primary human breast cancers are estrogen-dependent and express both estrogen (ER) and progesterone receptors (PR). Whereas expression of the two naturally occurring PR isoforms, PR-A and PR-B, is close to equimolar in normal human tissues, the ratio of the two receptors varies extensively in tumors. This is important since the two PR are functionally distinct and have differential repressor effects on ER. The PR isoform content may, therefore, affect the outcome of endocrine therapies targeted at ER. Study of PR isoforms is difficult because the two receptors are co-expressed in cells under estradiol stimulation. We have engineered four sets of T47D human breast cancer cells that, independent of estrogen: (i) express only PR-A; (ii) express only PR-B; (iii) are PR-negative; or (iv) contain both PR isoforms. Each of these cell lines was grown into solid tumors in nude mice in a strictly 17beta-estradiol-dependent manner. Results show, first, that PR-A expressing cells grow into tumors that are approximately half the size of PR-B expressing tumors, and second, that the reduced growth of PR-A tumors occurs in the absence of PR ligand. Tamoxifen treatment preferentially inhibited the growth of PR-A tumors, whereas PR-B tumors were unaffected. Thus, PR are not just passive markers of functional ER; the prevalence of PR-A or PR-B may differentially influence tumor phenotype.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available