Beta 5 integrin subunit
(ITGB5)

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Gene: ITGB5 maps to .
mRNA: size: 3.3-3.4 kb. Beta 5 mRNA was found in seven very different cell lines (McLean J.W. et al., 1990). Other investigators found this messenger in carcinoma, hepatoma, and fibroblast cell lines, but not in lymphoblastoid cells and platelets (Ramaswamy H. and Hemler M.E., 1990).
Protein: the ITGB5 cDNA codes for a 775 amino acids (aa) mature protein with a hydrophobic leader sequence of 24 aa (McLean J.W. et al., 1990). The beta 5 sequence resembles the beta 3, beta 2, and beta 1 sequences by 55%, 43%, and 38%, respectively.

Cell lines:
- A blocking antibody to the alpha_Vbeta₅ integrin (a vitronectin receptor) was shown to inhibit migration of MCF-7 cells in response to insulin-like growth factor-1 (IGF-I) through vitronectin but not through type IV collagen (Doerr M.E. and Jones J.I., 1996).

- Purified bone sialoprotein (BSP), recombinant human BSP fragments and BSP-derived RGD peptides were shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 BCC line. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha_Vbeta₃ vitronectin receptor, whereas adhesion and proliferation responses were alpha_Vbeta₅-mediated (Sung V. et al., 1998).

- MCF-7 BCC were shown to exhibit a urokinase-dependent physical association between uPAR and the vitronectin receptor alpha_Vbeta₅. These BCC responded to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that were mediated by alpha_Vbeta₅ and required protein kinase C activity. On the contrary, binding of vitronectin to alpha_Vbeta₅ resulted in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, alpha_Vbeta₅ was required for urokinase-directed, receptor-dependent MCF-7 BCC migration (Carriero M.V. et al., 1999).

- Alpha_Vbeta₃ was found to be highly expressed on MCF-7 BCC transfected with protein kinase C-alpha (MCF-7-PKC-alpha BCC), but was undetectable on MCF-7V BCC (MCF-7 BCC transfected with vector only). In contrast, MCF-7-PKC-alpha BCC had reduced expression of alpha_Vbeta₅. Blocking experiments with antibodies to alpha_Vbeta₃ and alpha_Vbeta₅ revealed that these receptors were used by MCF-7-PKC-alpha BCC to adhere primarily to vitronectin and osteopontin. Consistent with heterodimer expression, MCF-7-PKC-alpha cells expressed increased beta₃ and decreased beta₅ on their surface. Surface expression of alpha_V on MCF-7-PKC-alpha BCC was unchanged. Western blotting, Northern analysis, and nuclear run-on assays indicated that post-translational mechanisms increased the surface expression of beta₃ on MCF-7-PKC-alpha BCC. In contrast, reduced beta₅ transcription diminished beta₅ surface expression on MCF-7-PKC-alpha BCC (Carey I. et al., 1999).

Tumors:
- Alpha V/Beta 5 is an integrin that structurally and functionnally resembles Alpha V/Beta 3 (vitronectin receptor) and recognizes similar ligands. Contrasting with Alpha V/Beta 3, Alpha V/Beta 5 was not found in normal breast, primary carcinoma, or skeletal metastases (Liapis H. et al., 1996).

- Studies have indicated that uPAR could be associated in large molecular complexes with other molecules, such as integrins. In a study of 10 human breast carcinomas, the ability of uPAR to physically associate with the vitronectin receptor alpha_Vbeta₅ was shown (Carriero M.V. et al., 1999).

Carey I. et al. (1999) Overexpression of protein kinase C-alpha in MCF-7 breast cancer cells results in differential regulation and expression of alphavbeta3 and alphavbeta5. Int. J. Oncol. 15, 127-136.
Carriero M.V. et al. (1999) Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer. Cancer Res. 59, 5307-5314.
Doerr M.E. and Jones J.I. (1996) The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells. J. Biol. Chem. 271, 2443-2447.
Liapis H. et al. (1996) Integrin alpha_Vbeta₃ expression by bone-residing breast cancer metastases. Diagn. Mol. Pathol. 5, 127-135.
McLean J.W. et al. (1990) cDNA sequence of the human integrin beta 5 subunit. J. Biol. Chem. 265, 17126-17131.
Ramaswamy H. and Hemler M.E. (1990) Cloning, primary structure and properties of a novel human integrin ß subunit. EMBO J. 9, 1561-1568.
Sung V. et al. (1998) Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha(v)beta3 and alpha(v)beta5 integrins. J. Cell Physiol. 176, 482-494.

About integrins, beta 1, beta 3, alpha V