Bud10p directs axial cell polarization in budding yeast and resembles a transmembrane receptor.

BACKGROUND: The budding yeast Saccharomyces cerevisiae can bud in two spatially programmed patterns: axial or bipolar. In the axial budding pattern, cells polarize and divide adjacent to the previous site of cell separation, in response to a cell-division remnant, which includes Bud3p, Bud4p and septin proteins. This paper investigates the role of an additional component of the cell-division remnant, Bud10p, in axial budding. RESULTS: The sequence of Bud10p predicts a protein that contains a single trans-membrane domain but lacks similarity to known proteins. Subcellular fractionations confirm that Bud10p is associated with membranes. Bud10p accumulates as a patch at the bud site prior to bud formation, and then persists at the mother-bud neck as the bud grows. Towards the end of the cell cycle, the localization of Bud10p refines to a tight double ring which splits at cytokinesis into two single rings, one in each progeny cell. Each single ring remains until a new concentration of Bud10p forms at the developing axial bud site, immediately adjacent to the old ring. Certain aspects of Bud10p localization are dependent upon BUD3, suggesting a close functional interaction between Bud10p and Bud3p. CONCLUSIONS: Bud10p is the first example of a transmembrane protein that controls cell polarization during budding. Because Bud10p contains a large extracellular domain, it is possible that Bud10p functions in a manner analogous to an extracellular matrix receptor. Clusters of Bud10p at the mother-bud neck formed in response to Bud3p (and possibly to an extracellular cue, such as a component of the cell wall), might facilitate the docking of downstream components that direct polarization of the cytoskeleton.

Human testicular cancer. Changes in autosomal dosage.

Fourteen males with testicular tumor were studied by Southern blot hybridization. Probes detecting restriction fragment length polymorphisms at loci on 14 autosomes were used. In comparison with DNA from normal tissue, clear differences in allele dosage were observed in tumor DNA at loci mapping to the short and/or long arm of chromosomes 5, 7, and 12 in six patients with testicular germ cell tumor. In three patients, all three chromosomes were affected. Tumor DNA of the same patients also showed an imbalance between the sex chromosomes, with a relative deficiency of DNA of Y-chromosomal and a concurrent excess of DNA of X-chromosomal origin. Restriction fragment length polymorphisms from chromosomes 1, 3, 9, 11, 13, 16, 17, 18, 19, 21, and 22 did not show any consistent changes in tumor DNA. Possible consequences of the above alterations as a result of gene dosage effects, oncogene activation, and unmasking of tumor suppressor genes are discussed.

Results of treatment in irradiated testicular seminoma patients.

Excellent treatment results have been achieved historically with postoperative radiotherapy in testicular seminoma. In this retrospective study the treatment results of 211 patients with Stage I-II testicular seminoma treated in Finland during the years 1970-1983 were evaluated. 176 (84%) patients received postoperative radiotherapy alone. In addition to radiotherapy, 26 (12%) patients received chemotherapy during the primary treatment. There were 129 Stage I (61%), 66 Stage IIA-B (31%) and 16 Stage IIC (8%) tumors. The 5-year survival rate was 95% in Stage I, 87% in Stage IIA-B and 73% in Stage IIC. In Stage I, seven relapses (relapse rate 6%) occurred after irradiation; three of them were cured with second-line therapies. None of the relapses occurred within the radiotherapy field. In Stage IIA-B, 31 patients had only parailiacic + aortic irradiation, 25 patients received both parailiacic + aortic and mediastinal irradiation. With both radiotherapy techniques there was no significant difference in the number of relapses (seven and three) and in the remission rate (94% and 96%). Radiotherapy alone was used on four Stage IIC patients and one of them died during the primary treatment. Two of them relapsed, but could be cured with chemotherapy. These results correspond to those reported in the literature and they suggest that prophylactic mediastinal irradiation is unnecessary in Stage IIA-B patients. Stage IIC patients should receive chemotherapy initially.

Molecular studies of the sex chromosomes in human testicular cancer: pronounced changes in X and Y chromosome dosage in some tumors.

Nine males with testicular germ cell tumors were studied by Southern blotting using probes recognizing different regions of the X and Y chromosomes. In the tumors of three patients, an imbalance was noted with a relative deficiency of DNA of Y-chromosomal and a concurrent excess of that of X-chromosomal origin. The X:Y signal ratios were 4, 4, and 2, respectively, in tumor DNA relative to normal DNA, and the ratios of Y to an autosomal locus were 0.4, 0.6, and 0.7, respectively, in the same tumors. Several loci on both arms of the Y chromosome were similarly involved. No structural abnormalities of Y chromosome DNA could be demonstrated. The X/Y change occurred in two of the three patients with nonseminomatous tumors and in two of the three patients with metastatic disease. To account for the results, two alternative models are discussed: first, loss of the Y chromosome and increase in X chromosome number in some but not all tumor cells; second, polyploidization with one Y chromosome and several X chromosomes.

Morphology of testicular germ cell tumours in treated and untreated cryptorchidism.

The histology of 75 testicular germ cell tumours in 73 patients with treated or untreated cryptorchidism was investigated in a group of 503 patients with testicular germ cell tumour and evaluated according to the WHO classification. The proportion of pure seminoma was associated with the height of the testis, being 87% in abdominal. 78% in inguinal and 50% in normally positioned testes. In patients operated upon for cryptorchidism, the current site of the testis seemed to be a more important determinant of this proportion than the original site. The proportion of pure seminoma which developed in testes after successful orchiopexy was equal to that in normally-descended testes (50%) and lower (39%) if orchiopexy had been performed before the age of 16 years. Similarly, among non-seminomas, a higher proportion of tumours containing teratoma tissue was found in cryptorchidism was successfully treated in childhood. It was concluded that a successful orchiopexy in childhood decreases especially the risk of seminoma.

Trends in incidence and results of treatment of testicular germ cell tumours in Finland 1972-1983.

A nationwide series of 422 patients with testicular germ cell cancer diagnosed in Finland in 1972-1983 was analysed. The age-adjusted incidence rate, although very low (1.6 per 10(5) male population per year), has increased compared to that in previous decades. The 3-year survival rate has improved markedly and was during the last part of the period high in patients with local (stage I) and regional (stages IIA-B) disease (100% for seminoma and over 90% for non-seminoma patients) but still fairly poor in advanced stages (stages IIC-IV) (58% for seminoma and 26% for non-seminoma patients). The improvement of the survival rate was most marked in non-seminoma patients below the median age (28.5 years). Cisplatin based chemotherapy was one of the major reasons for the improved prognosis, not only in non-seminoma patients but also in those with seminoma. There was no trend with time concerning the stage distribution of the disease. On the basis of relapse rates in stage I non-seminoma and seminoma patients staged surgically and clinically respectively, accuracy of clinical staging but not of surgical staging seemed to have improved. During the early period surgically staged stage I-II non-seminoma patients had a slightly better prognosis than clinical stage I-II patients but a similar difference was not observed during the cisplatin era.