Children's Medical Center Corporation

Pintex Pharmaceuticals, Inc.

Children's Medical Center of Boston

Lere Bao

Bruce R Zetter

Da Gong Wang

Jacqueline Banyard

We have discovered a protein in humans, herein referred to as collagen like gene (CLG) product (SEQ ID NOS: 12 and 13), that is expressed in human prostate cancer and breast cancer cell lines but not in normal adult, placenta, lung, liver, skeletal muscle, kidney or pancreas tissues. We have also discovered that the level of CLG mRNA expression correlates positively with the metastatic potential of the cancer cell lines tested.

Methods for diagnosis and prognosis of cancer

This invention provides methods for diagnosing prostate cancer, methods for measuring the aggressiveness of prostate cancer, and methods for identifying prostate cancer likely to metastasize. The diagnostic and prognostic assays of this invention include methods involving the antibody-based detection of Pin1 and the amplification of Pin1 RNA. The diagnostic and prognostic assays of this invention may be used in combination with other methods of prostate cancer diagnosis including the PSA test, digital rectal exam, and Gleason prostate tumor grading system.

Pin 1 as a marker for prostate cancer

The present invention provides a thymosin &bgr;15 promoter. The promoter comprises the nucleotide sequence of SEQ ID NO:1 or a fragment thereof capable of expressing an operably linked DNA. A DNA sequence having nucleotides &minus;400 to &plus;1 of FIG. is a preferred fragment. The invention also provides novel assays for identifying compounds useful in the treatment of malignancies involving modulation of thymosin &bgr;15 expression, e.g., breast, pancreas and prostate cancer. The invention further provides a method of human gene therapy for treating malignancies involving up-regulation of thymosin &bgr;15 expression.

Thymosin &bgr;-15 promoter and uses thereof

The present inventors have now discovered that humans have a gene that encodes a novel protein of the thymosin &bgr; family. This novel protein, herein referred to as thymosin &bgr;15, has the ability to bind and sequester G-actin, like other members of the thymosin &bgr; family, but unlike what is known about other members it also directly regulates cell motility in prostatic carcinoma cells. The present invention is direct to an isolated cDNA encoding the human thymosin &bgr;15 gene (SEQ ID NO: 1) and have deduced the amino acid sequence (SEQ ID NO: 2).

Antibodies specific for human thymosin &bgr;15 protein and uses thereof

The present inventors have discovered that humans have a gene that encodes a novel protein of the thymosin .beta. family. This novel protein, herein referred to as thymosin .beta.15, has the ability to bind and sequester G-actin, like other members of the thymosin .beta. family, but unlike what is known about other members also directly regulates cell motility in prostatic carcinoma cells. A cDNA of the human thymosin .beta.15 gene (SEQ ID NO: 1) and having the deduced the amino acid sequence (SEQ ID NO: 2) was isolated. The present inventors have shown that enhanced transcripts (mRNA) and expression of the thymosin .beta.15 gene in non-testicular cells has a high correlation to disease state in a number of cancers, such as prostate, lung, melanoma and breast cancer, particularly metastatic cancers. Accordingly, discovering enhanced levels of transcript or gene product in non-testicular tissues can be used in not only a diagnostic manner, but a prognostic manner for particular cancers.

Method for diagnosis of cancer

The present inventors have now discovered that humans have a gene that encodes a novel protein of the thymosin .beta. family. This novel protein, herein referred to as thymosin .beta.15, has the ability to bind and sequester G-actin, like other members of the thymosin .beta. family, but unlike what is known about other members it also directly regulates cell motility in prostatic carcinoma cells. The present invention is direct to an isolated cDNA encoding the human thymosin .beta.15 gene (SEQ ID NO: 1) and have deduced the amino acid sequence (SEQ ID NO: 2).

Human thymosin .beta.15 gene, protein and uses thereof

Method for prognosis of prostate cancer

Human thymosin .beta.15

The present inventors have now discovered that humans have a gene that encodes a novel protein of the thymosin .beta. family. This novel protein, herein referred to as thymosin .beta.15, has the ability to bind and sequester G-actin, like other members of the thymosin .beta. family, but unlike what is known about other members it also directly regulates cell motility in prostatic carcinoma cells. The present invention is directed to an isolated cDNA encoding the human thymosin .beta.15 gene (SEQ ID NO: 1) and have deduced the amino acid sequence (SEQ ID NO: 2).

Growing community of inventors

Brookline, MA, United States of America

Lere Bao