Iatrogenic acute estrogen deficiency and psychiatric syndromes in breast cancer patients.

The change of estrogen function, represented by amenorrhea or hot flashes, that results from breast cancer treatment may increase the risk of major depressive disorder in those women undergoing treatment for breast cancer. This pilot study describes the course of menopausal symptoms and the incidence of depression in 21 patients who were likely to become acutely estrogen deficient during treatment for breast cancer. These included women who lost menses during chemotherapy, who suddenly stopped estrogen replacement therapy (ERT), or who started tamoxifen. Eight patients (38%) developed major depressive disorder, the majority within 6 months of starting treatment. Twenty patients (95%) had dysphoria and/or insomnia. Fourteen patients (66%) had hot flashes. While this is only pilot data, these data suggest that breast cancer patients whose treatment precipitates menopausal symptoms should be targeted for diagnosis of depression and treated if diagnosed.

Activation by heat shock of hsp70 gene transcription in sea urchin embryos.

We had previously shown that P. lividus embryos subjected to heat shock are unable to synthesize proteins of the hsp70 family at a detectable level before the hatching blastula stage. We show here that this is not due to the inability to synthesize the hsp70 mRNAs, which are detectable following heat shock also in early stages, although in much lower amounts per embryo than in later stages. These mRNAs are also translated, as judged by the facts that they are present in the polysomal pellet, and that they are translatable in a cell free system. As to the question of the amount of hsp70 RNAs per nucleus, we conclude that this is also higher in later than in earlier stages. The presence of hsp70 mRNAs is already detectable after heating at 4 centigrades above 20 and their amount increases with the increase of temperature in the range between 24 degrees C and 28 degrees C.

Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.

We have previously reported on the identification of a cDNA (placenta growth factor, PlGF) coding for a novel angiogenic factor expressed in placental tissue that is similar to vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). Biochemical and functional characterization of PlGF derived from transfected COS-1 cells revealed that it is a glycosylated dimeric secreted protein able to stimulate endothelial cell growth in vitro. Here, we report the isolation and characterization of the PlGF gene located on chromosome 14. At least two different mRNAs are produced from this single-copy gene in different cell lines and tissues. Sequence comparison of the polypeptides encoded by the two different isolated cDNAs indicates that they are identical except for the insertion of a highly basic 21 amino acid stretch at the carboxyl end of the protein. RNA expression analysis of several tissues, tumors and cell lines indicates differential distribution of the two PlGF mRNAs. Finally, preliminary results indicate that the PIGF gene has been conserved in evolution, since the human PlGF cDNA hybridizes to sequences present in the genomic DNA of Drosophila, Xenopus, chicken and mouse.

Characterization of a new member of the sea urchin Paracentrotus lividus hsp70 gene family and its expression.

We have sequenced a second gene of the hsp70 family derived from a genomic clone of the sea urchin, Paracentrotus lividus. The structure of this gene, named hsp70IV gene, is interrupted by one intron and differs from the previously analyzed sea urchin hsp70II gene, which contains several introns. Two open reading frames of hsp70IV gene encode a predicted protein of 639 amino acids with an M(r) of 69,672. The 5' flanking region of the gene contains a putative TATA element, three heat-shock elements made up of some arrays of the 5-bp units, NGAAN and NTTCN (N = A,C,G or T), a canonic consensus sequence for binding of the regulatory activating transcription factor (ATF), and a purine box. The 3' flanking region contains four putative polyadenylation sites located at different sites downstream from the stop codon. Using Northern blot hybridization analysis, carried out using a probe corresponding to a 3' noncoding fragment (UTR) peculiar to hsp70IV gene, we found that this gene is transcribed only under heat shock (Hs) and that the transcript can be recovered from the polysomal pellet. The hsp70IV gene may be classified as a Hs gene 70 although it contains one intron.

Stress proteins by zinc ions in sea urchin embryos.

In Paracentrotus lividus embryos, treatment with zinc ions induces the synthesis of the two major stress proteins with the same molecular weight as those induced by heat shock. The developmental stages responsive to zinc ion treatment are the same as those responsive to heat shock. However, zinc treatment induces a longer lasting synthesis of the stress proteins, and, unlike heat shock, does not induce thermotolerance and does not inhibit synthesis of the bulk proteins.