p96, a MAPK-related protein, is consistently downregulated during mouse mammary carcinogenesis

Differential display PCR [DD-PCR] was applied to identify mRNAs differentially expressed between two consecutive stages of an in vivo model of mouse mammary carcinogenesis. The extended life 12 [EL12] and transformed mammary 12 [TM12] outgrowths differ in morphology, ovarian hormone dependence, and tumorigenicity, yet the TM12 outgrowth arose spontaneously from the EL12 outgrowth. A fragment of the mouse p96 gene was identified using DD-PCR. The differential expression of p96 was confirmed using RNase protection assays. Examination of the RNA expression patterns of the p96 isoforms during normal mammary gland development showed high levels in the involuting mammary gland and in preneoplastic hyperplasias. In contrast, p96 isoform mRNA levels were consistently decreased in mammary tumors derived from the in vivo hyperplasias. Examination of p96 protein levels revealed a decrease in p96 protein in a number of mammary tumors as compared to their hyperplastic precursors further supporting the observations that p96 gene expression is consistently downregulated in mammary tumors. The functional activity of p96 protein has not been resolved, however the observation that p96 gene expression is downregulated in two different tumor systems (human ovarian tumors and mouse mammary tumors) warrants more extensive investigation on its role in normal and neoplastic cell growth.