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CD4− epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green fluorescent protein gene as a reporter gene to demonstrate that HIV-1 can infect some CD4− human epithelial cell lines with low but significant efficiencies. Importantly, HIV-1 infection of these cell lines is independent of HIV-1 envelope proteins. The Env-independent infection of CD4− cells by HIV-1 suggests an alternative pathway for HIV-1 transmission. Even on virions bearing Env, a neutralizing antibody directed against gp120 is incapable of neutralizing the infection of these cells, thus raising potential implications for HIV-1 vaccine development.

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The prostate -specific antigen ( PSA ) promoter is known to be highly tissue specific. Although its tissue specificity has been confirmed, its efficiency of gene transcription is significantly lower compared to known nonspecific viral promoters. These lower levels of promoter activity therefore pose a problem when developing an efficacious gene vector for prostate cancer gene therapy. Thus, selecting an appropriate therapeutic gene and vector system to carry the gene driven by the PSA promoter ( PSAP ) is important. In the studies described here, a human immunodeficiency virus ( HIV ) -1 -based lentiviral vector carrying either the enhanced green fluorescent protein ( EGFP ) reporter or the diphtheria toxin A ( DTA ) gene was constructed. The results demonstrate that the PSA promoter in a lentiviral vector drives genes in prostate cells with satisfactory efficacy and specificity. The tissue -specific expression of the DTA protein efficiently eradicates LNCaP prostate cells in culture. We also infected prostate cancer cells and control cells carried by nude mice with the EGFP lentiviral vector. Significant numbers of EGFP -positive LNCaP cells were detected in all the mice bearing these tumors, but no EGFP -positive control cells were detected in any other mouse tissue. The high levels of expression in prostate cells, compared with the low levels of background expression in other cells, show that the PSAP -lentiviral vector could be a potential useful tool for gene therapy of metastatic prostate cancer. Cancer Gene Therapy ( 2001 ) 8, 628 -635

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Claudins are a family of proteins involved in forming tight junctions between cells. Here we describe two forms of claudin-7 (CLDN-7), a full-length form of CLDN-7 with 211 amino-acid residues and a C-terminal truncated form with 158 amino-acid residues. These two forms of CLDN-7 are able to regulate the expression of a tissue-specific protein, the prostate-specific antigen (PSA), in the LNCaP prostate cancer cell line. We also found that the expression of CLDN-7 is responsive to androgen stimulation in the LNCaP cell line, suggesting that this protein is involved in the regulatory mechanism of androgen. Both forms of claudin-7 are expressed in human prostate, kidney and lung samples, and in most samples, the full-length form of claudin-7 was predominant. However, in some prostate samples from healthy individuals, the truncated form of claudin-7 is predominantly expressed. Our results demonstrated that unlike other claudins, CLDN-7 has both structural and regulatory functions, and the two forms of CLDN-7 may be related to cell differentiation in organ development.

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