Using a fragment of the estrogen receptor (ER) cDNA as a probe, Southern blots of HindIII-digested genomic DNA, from breast tumours and non-cancerous tissue, revealed a 1.6 kb hybridizing fragment (1.6KbHF) in 3 out of 30 tumours, and in 31 out of 80 mastectomy samples (16 sectors from each of 5 patients), which was significantly correlated with the absence of progesterone receptor.
Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors.
The response to endocrine therapy is not entirely predictable from the estrogen receptor (ER) and progesterone receptor (PgR) status of primary breast tumors.
In summary, in PR-positive breast tumors the ratio of expression of PR A and B proteins is close to unity as is seen in a number of other progestin target tissues.
Three methylation-sensitive restriction sites in the PR gene CpG island are not methylated in normal breast specimens and PR+ human breast cancers but are hypermethylated in 40% of PR- human breast tumors.
The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets.
The aim of this study was to measure osteonectin mRNA and protein expression in breast tumour biopsies and compare these with oestrogen (ER) and progesterone receptor (PR) levels in the same tumours.
The expression of this variant was significantly higher (relative to ER) in untreated ER-positive breast tumours which were both progesterone receptor (PgR) negative and pS2 negative phenotype.
Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins.
In order to determine whether changes in D6-PR variant expression could occur during tumorigenesis, its expression was investigated by reverse transcription and polymerase chain reaction in ten normal reduction mammoplasty samples, nine breast tumours with high PR levels (> 100 fmol mg(-1) protein) and eight breast tumours with low PR levels (< 15 fmol mg(-1) protein), as determined by ligand binding assay.
The common profile of alternatively spliced ER and PR transcripts in breast tumors means that this feature cannot be used as a discriminator of hormone responsiveness or other clinical end points.
An absolute and relative increase in ER-beta mRNA levels in ER negative and PR negative breast tumors, which rarely respond to endocrine therapy, suggests the possible involvement of up-regulation of ER-beta mRNA in the development of estrogen-independent tumors.
The authors found that 13 of 14 primary breast tumors (93%) with mutant p53 protein overexpression were estrogen receptor negative (P = 0.01) and 11 of 14 (79%) were progesterone receptor negative (P = not significant).
Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues.
Because low or absent PR in primary breast cancer is associated with poor prognosis and response to hormone therapy, our results suggest that low PR status may serve as an indicator of activated growth factor signaling in breast tumor cells, and therefore of an aggressive tumor phenotype and resistance against hormonal therapy.