The sodium/iodide symporter mediates active iodide transport in both healthy and cancerous thyroid tissue. By exploiting this activity, radioiodide has been used for decades with considerable success in the detection and treatment of thyroid cancer. Here we show that a specialized form of the sodium/iodide symporter in the mammary gland mediates active iodide transport in healthy lactating (but not in nonlactating) mammary gland and in mammary tumors. In addition to characterizing the hormonal regulation of the mammary gland sodium/iodide symporter, we demonstrate by scintigraphy that mammary adenocarcinomas in transgenic mice bearing Ras or Neu oncogenes actively accumulate iodide by this symporter in vivo. Moreover, more than 80% of the human breast cancer samples we analyzed by immunohistochemistry expressed the symporter, compared with none of the normal (nonlactating) samples from reductive mammoplasties. These results indicate that the mammary gland sodium/iodide symporter may be an essential breast cancer marker and that radioiodide should be studied as a possible option in the diagnosis and treatment of breast cancer.

SummaryIn Aspergillus nidulans a highly specific L-proline transporter is encoded by the prnB gene which is tightly linked to all other genes involved in proline catabolism. In mycelia, the expression of the prn structural genes is finely co-regulated in response to proline induction and nitrogen/carbon catabolite repression. In this study we establish that prnB expression is also activated during germination of conidiospores. This activation persists until the development of 6 h-old mycelia and it is independent of proline induction mediated by the pathway-specific prnA gene product. We then show that, in mycelia, prnB transcription is activated in response to proline or histidine starvation. This process has two components: a prnA-dependent and a prnA-independent component. A cis-acting element that conforms to the consensus target of the GCN4/CPC1 transcriptional activators mediating amino acid biosynthesis activation in other fungi is involved in the activation of prnB transcription in response to amino acid starvation. We also show that the stimulation of prnB expression in germinating conidiospores is not due exclusively to transient internal amino acid starvation occurring during the transition from conidiospore to mycelium. This is the first report that an amino acid transporter gene is upregulated during development and in response to amino acid starvation and specific amino acid induction.

In the filamentous fungus Aspergillus nidulans, L-proline uptake is mediated by the product of the prnB gene which codes for a member of a family of amino acid transporters found both in pro- and eukaryotes. Regulation of prnB gene expression has previously been studied in great detail at the molecular level. However, no studies have addressed possible post-transcriptional controls or the kinetic characterisation of the PrnB transporter. Here we develop a rapid and efficient method for direct uptake measurements of proline in germinating conidiospores of A. nidulans. We make use of this method and Northern blot analyses in parallel to study the regulation of PrnB expression both at the level of prnB message accumulation and at a post-transcriptional level. These studies show that (i) pathway-specific and wide-domain regulatory systems, previously shown to control prnB gene expression in multicellular mycelia, also operate in unicellular conidia committed to germination; and (ii) PrnB activity is regulated in response to the nitrogen source present in the medium and the level of internally accumulated proline or other amino acids. We also characterise kinetically the PrnB transporter and a secondary proline transport system. Our results open new possibilities for studies using unicellular conidiospores of filamentous fungi and constitute a necessary first step for a subsequent structure-function analysis of the PrnB transporter.

Abstract:We propose and demonstrate the use of short pulsed fiber lasers in surface texturing using MHz-repetition-rate, microjoule-and sub-microjoule-energy pulses. Texturing of titanium-based (Ti6Al4V) dental implant surfaces is achieved using femtosecond, picosecond and (for comparison) nanosecond pulses with the aim of controlling attachment of human cells onto the surface. Femtosecond and picosecond pulses yield similar results in the creation of micron-scale textures with greatly reduced or no thermal heat effects, whereas nanosecond pulses result in strong thermal effects. Various surface textures are created with excellent uniformity and repeatability on a desired portion of the surface. The effects of the surface texturing on the attachment and proliferation of cells are characterized under cell culture conditions. Our data indicate that picosecond-pulsed laser modification can be utilized effectively in low-cost laser surface engineering of medical implants, where different areas on the surface can be made cell-attachment friendly or hostile through the use of different patterns. 192-203 (1997) Lett. 17, 733-737 (2004). 25. S. P. S. Porto, P. A. Fleury, and T. C. Damen, "Raman spectra of TiO2, MgF2, Zn F2, FeF2, and MnF2," Phys. Rev. 154, 522-526 (1967

The function of sodium iodide symporter (Na + /I À symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I À in milk; the newborn's first source of I À for thyroid hormone synthesis. Furthermore, increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS. In this study, using breast cancer cell lines, we established that tRA-responsive NIS expression is confined to estrogen receptor-a (ERa) positive cells and we investigated the role of ERa in the regulation of NIS expression. We showed that the suppression of endogenous ERa by RNA interference downregulates NIS expression in ERa positive mammary cells. Besides, in an ERa negative cell line, reintroduction of ERa resulted in the expression of NIS in a ligand-independent manner. We also identified a novel estrogen-responsive element in the promoter region of NIS that specifically binds ERa and mediates ERa-dependent activation of transcription. Our results indicate that unliganded ERa (apo-ERa) contributes to the regulation of NIS gene expression. In mammary gland lactocytes, sodium/iodide (Na + /I À ) symport via NIS is required to secrete I À in mother's milk [1]. I À in milk is used by the newborn in thyroid hormone biosynthesis, and thus it plays an essential role in post-natal development of skeletal muscles, nervous system, and lungs [2]. In vivo experiments in mice have previously demonstrated that in normal physiology, NIS expression is strictly linked to mammary development in gestation, and to lactation [1]. Non-lactating mammary gland tissue in female mice does not express NIS unless animals receive subcutaneous oxytocin treatments for three consecutive days. On the other hand, a similar treatment in ovariectomized mice is not sufficient for NIS upregulation. In these surgically treated animals, administration of 17-b-estradiol (E2) together with oxytocin is essential for functional expression of NIS. The fact that E2 treatment was only essential in ovariectomized animals, whereas lactogenic hormones were sufficient for functional NIS expression in surgically untreated mice, suggested that ovary functions and endogenous estrogens are essential in upregulating NIS expression [1]. Unlike in non-lactating mammary gland tissue, in transgenic mice bearing experimental breast cancers triggered by Erb-B2/neu and ras oncogenes, functional expression of NIS significantly increases [1]. In the same study, human breast cancer specimens were also analyzed, and an increased NIS expression was detected in human invasive breast cancer and ductal carcinoma in situ, as compared to no expression of NIS in healthy breast samples obtained from reductive mammoplasty operations [1].Recent studies with an ERa+ mammary cell line model, MCF-7, have led to the identification of additional hormones or ligands that control transcriptional regulation of NIS. In this cell line, the symporter gene was shown to be indu...