Endocrine Oncology (Contemporary Endocrinology) by Stephen P. Ethier

By Stephen P. Ethier

Stephen P. Ethier and a panel of major investigators comprehensively learn the mobile, molecular, and endocrine elements within the improvement of cancers of the breast, prostate, endometrium, and ovary. targeting defining crucial unresolved concerns within the box, the authors evaluation how steroid hormones functionality to manage common mammary gland homeostasis in people, with specific emphasis at the roles of estrogen, progesterone, and progress elements. complete and updated, Endocrine Oncology bargains either uncomplicated and scientific researchers not just the most recent molecular and mobile findings on endocrine cancers, but in addition a strong serious research that may turn out necessary to all endocrinologists and oncologists operating within the quarter at the present time.

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Cancer Res 1991;51:105–109. 37. Daffada AA, Johnston SR, Smith IE, Detre S, King N, Dowsett M. Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer. Cancer Res 1995;55:288–293. 38. Zhang QX, Borg A, Fuqua SA. An exon 5 deletion variant of the estrogen receptor frequently coexpressed with wild type estrogen receptor in human breast cancer. Cancer Res 1993;53:5882–5884. 39. Desai A, Luqmani Y, Coope R, Dagg B, Gomm J, Pace P, et al.

The exon-deleted ER_ mRNAs have been identified mostly from reverse transcription polymerase chain reaction (RT-PCR) products, using targeted primers. Multiple ER_ variant mRNAs are often detected in individual tumor specimens. In order to determine the relative frequency and pattern of variant expression in a particular sample, an RT-PCR approach was developed that allowed the simultaneous detection of all deleted ER_ variant mRNAs containing the primer annealing sites in exons 1 and 8, at levels that represent their initial relative representation in the RNA extract.

Therefore, depending on the antibodies (Abs) used, the presence of C-terminally truncated ER_ variant proteins could theoretically influence determination of ER status of the tumor sample. The authors have tested this experimentally, by transiently transfecting WT ER_ and clone-4-truncated ER_ expression vectors into Cos-1 cells, and determining ER status of the cells, using Abs either to the N-terminus of the ER_ (Fig. 3, 1D5, Dako) or Abs to the C-terminus (Fig. 3, AER311, Neomarkers). Preliminary data, using Chapter 2 / ER in Human BC 25 different combinations of WT ER_ and variant ER_ expression vectors transfected into Cos-1 cells, indicate that the signals (expressed as H-scores, which take into account the intensity of staining and the number of positively staining cells) obtained with the Nterminal and C-terminal Abs, become increasing discrepant (N-terminal > C-terminal signal) with increasing variant expression, presumably because of increased ER_-like proteins containing the N-terminal region, but not the C-terminal region.

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