ABSTRACT
Polyomavirus, a DNA tumor virus, expresses three viral oncoproteins (large, middle and small T antigens), causes malignant transformation in cell culture and induces multiple tumors in vivo. The middle T (MT) antigen seems to play an essential role in transformation and tumori-genicity. The observation that MT-overexpressing cell lines are able to grow in the absence of PDGF (platelet-derived growth factor) led several laboratories to study the mechanism underlying MT-induced growth deregulation and the signal transduction pathway used by this viral oncoprotein. A number of cellular proteins were shown to be common to both the normal PDGF mitogenic pathway and the MT transforming pathway. The expression of some PDGF primary response genes (fos, jun, myc, JE, KC) was shown to be rendered constitutive by MT overexpression. Using MT mutants, important domains for binding and activation of cytoplasmic proteins were mapped. Wild type and mutant MT cell lines are used in our laboratory to analyze the expression and activity of the PDGF early response genes during cell transformation and correlate them with activation of specific cytoplasmic proteins. In addition to abrogating the PDGF requirement for growth, activation of cellular proteins caused by MT results in cell lines that have an altered morphology and are able to form colonies in agarose. These changes may be due to alterations in connexin 43 and other cell surface proteins.
Subject(s)
Humans , Gene Expression/immunology , Platelet-Derived Growth Factor/genetics , Polyomavirus/genetics , Oncogenic Viruses/genetics , Polyomavirus/immunologyABSTRACT
El virus de polioma es capaz de inducir tumores en sus hospederos naturales y transformar células en cultivo. Por otro lado, el virus de papiloma humano se ha relacionado con diversos tipos de neoplasias; de manera particular con lesiones anogenitales humanas. No se conoce con exactitud el mecanismo a través del cual estos virus inducen transformación y tumorigénesis. El presente trabajo muestra algunas de las características de los mecanismos que utilizan los virus mencionados para participar en la transformación y tumorigénesis. Además, se ha encontrado que ciertos aspectos de la infección por el virus de polioma son parecidos a la infección del virus del papiloma (ambos pertenecen a la misma familia Papovaviridae), por lo que se consideran algunas semejanzas y diferencias entre los mismos
Polyomavirus is able to induce tumors in its natural host as well as to transform cells in cultures. On the other hand, human papillomavirus has been involved in several types of neoplasias such as anogenital lesions. Little is known about the mechanisms through which these viruses induce both transformation and tumorigenesis. The present work shows some characteristics of the mechanisms that papillomavirus and polyomavirus use to participate in tumorigenesis. It has also been noticed that the infection caused by polyomavirus resembles that performed by papillomaviruses (which belong to the same Papovaviridae family). Some similarities and differences between these viruses are considered.