PANG, A GENE ENCODING A NEURONAL GLYCOPROTEIN, IS ECTOPICALLY ACTIVATED BY INTRACISTERNAL A-TYPE PARTICLE LONG TERMINAL REPEATS IN MURINE PLASMACYTOMAS

Plasmacytomagenesis provides a murine model to decipher progressive ge netic events culminating in a B-cell neoplasia. Activation of the c-my c protooncogene by chromosomal translocation is considered an initiati ng event. Intracisternal A-type particles (IAPs) are defective retrovi ral-like structures present in the endoplasmic reticulum of plasmacyto mas (PCTs). IAP proviral insertions have been documented to engender n egative or positive effects on the expression of nearby cellular genes . We have isolated a gene, PANG (plasmacytoma-associated neuronal glyc oprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance t o axonal glycoproteins TAG-1 and F11 known to function in neuronal out growth. An extensive survey revealed a predominant 3.6-kb PANG transcr ipt in 60% (30 of 50) of PCTs as well as unique smaller and larger spe cies. All other normal and transformed lymphoid and nonlymphoid cell l ines and normal tissues were negative for PANG expression except for t he brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Re verse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.